pH响应型聚（α，β-L-天冬氨酸）衍生物的设计合成及其生物医学性能
|
摘要
当今化学疗法即“化疗”主要是指应用抗癌药杀灭体内癌细胞，从而达到治疗癌症的目的，其大多被当作手术的代替性手段以及手术后的铲草除根以及防止癌症复发手段使用。近年来，化疗发展的很快，但传统的抗肿瘤药物普遍存在半衰期短、对癌变组织选择性差、全身毒副作用大等缺点，大大限制了用药剂量和治疗效果，因此，设计良好的抗癌药物传递系统是肿瘤治疗过程中迫切需要解决的难题。抗肿瘤药物的理想载体应该具有以下的功能特点：良好的生物相容性和生物可降解性，载药量高，循环时间长，具有肿瘤特异性。
聚氨基酸类高分子材料因其良好的生物相容性、生物可吸收性及化学结构匹配性，在生物医用高分子领域有着无法比拟的优点和广泛的应用前景。特别是聚天冬氨酸，具有合成简单，成本较低，良好的生物相容性、生物降解性和可吸收性，易于功能化修饰等诸多优点。且在体内能够被逐渐吸收，其代谢产物对人体无毒，因而不会对周围组织、肝肾、血红细胞等产生毒副作用。因此聚天冬氨酸及其衍生物，被广泛用于药物载体的制备研究。关于聚天冬氨酸类载体已有很多报道，但是大部分的聚合物是通过N-羧酸酐（NCA）开环聚合方法合成得到聚(α-L-天冬氨酸)，这种方法制备的聚合物结构清晰明确，但合成步骤比较复杂，材料成本也相对提高。且一般认为聚-氨基酸二级结构过于规整，链段柔韧性差，不利于药物的扩散和释放。因此需要继续探索更为简便易行的可以实现肿瘤的特异性识别或富集或释放的响应性化学结构。本实验室以聚(α,β-L-天冬酰胺)为基本材料，设计具有环境刺激响应性能的生物降解高分子材料，并对其应用进行探索研究。
1）利用酸敏感的腙键将亲水的聚乙二醇和疏水性阿霉素键DOX合到聚天冬酰胺主链上，使得聚合物具有两亲性，再利用侧链键合的阿霉素与剩余游离阿霉素之间的疏水相互作用及-叠合作用将更多的阿霉素物理包埋到胶束内核。研究表明，通过调整DOX/Polymer的投料比，可以有效提高DOX的载药量，最高可达38%。该系列的纳米粒子稳定性好，体外实验表明，载有阿霉素的纳米粒子对阿霉素的释放具有良好的pH响应性。细胞结果表明载有阿霉素的纳米粒子保持了和自由阿霉素盐酸盐相近的药效。
2）以3-氨丙基咪唑和水合肼为亲核试剂，进攻聚琥珀酰亚胺进行开环反应得到氨丙基咪唑接枝聚天冬酰胺IM-g-PAHy。再利用醛化聚乙二醇PEG-CHO与肼基之间高效的反应形成腙键，得到侧链具有pH响应性官能团的两亲性聚合物mPEG/IM-g-PAHy，然后再将DOX通过腙键连接到聚合物骨架上，成功制备了得到了具有核可溶胀性的pH响应性阿霉素载药体系mPEG/IM-g-(PAHy-DOX)载药纳米粒子，并对其进行pH响应性、胶束形貌及释放动力学研究。研究发现，mPEG/IM-g-(PAHy-DOX)载药纳米粒子具有很好pH响应性，在pH7.4条件下，仅有少量释放，而在pH5.0条件下，最大释放量明显增加，且随着咪唑含量的增加，DOX的释放速度和释放量具有很大增加。但值得指出的是，随着聚合物中咪唑接枝度的增加，体系载药量也会随之降低。
3）生理条件下，利用腙键化学交联聚（α,β-L-天冬氨酸）衍生物原位制备水凝胶，成胶时间快，不需要加入任何小分子催化剂或交联剂。通过扫描电镜观察，水凝胶的内部均可以观察到致密、连贯的网络孔状结构。在模拟条件（pH=7.4和5.0，37℃）下，对聚（α,β-L-天冬氨酸）衍生物水凝胶进行降解行为研究发现，随着时间的推移水凝胶质量明显降低，28天降解35%-45%，说明该水凝胶具有很好的降解性能。以亲水性盐酸阿霉素为模型药物，研究了药物在该水凝胶中的装载和释放行为。在酸性环境pH时，阿霉素的释放速度的明显高于中性环境下的释放速度。根据Rigter-Peppas模型分析释放行为发现，在pH7.4生理条件下，阿霉素的释放遵循Fick扩机制，而在pH5.0酸性条件下，阿霉素在最初的释放过程中遵循无规扩散机制，即Fick扩散和高分子链的松弛协同作用结果。通过Hep G2细胞在水凝胶上的生长情况发现，该水凝胶支架有利于细胞的生长增殖。
4）设计了以-天冬氨酸为基本材料，对其聚合物侧链进行改性，制备了具有两性离子特性的聚氨基酸，作为具有pH敏感性的表面抗蛋白非特异性吸附材料，并对聚氨基酸的性质及等电点对抗蛋白质非特异性吸附能力的影响进行了系统的研究。
通过缩合反应制备得到的侧链部分接枝组氨酸HIS的聚（α,β-L-天冬氨酸）HIS-PAsp/PAsp，通过透过率、表面电势、酸碱滴定测试，证明其具有典型的两性离子特征。将其应用到无污染表面试验中可以看出，经静电吸附将HIS-PAsp/PAsp聚合物修饰到表面材料后纤维蛋白原的吸附量明显降低，且降低的程度与表面修饰的聚合物浓度有关。该材料有望成为一种很好的阳离子表面修饰材料。
通过氨基基团对聚琥珀酰亚胺（PSI）的开环反应引入弱碱性基团是一种效率高，条件可控的聚氨基酸衍生物制备方法。试验中制备了一系列具有不同等电点的两性离子叔胺化聚（α,β-L-天冬氨酸）DMPA-PAsp/Pasp。通过吸附试验证明，经静电吸附将不同等电点聚合物DMPA-PAsp/PAsp修饰到表面材料后对纤维蛋白原和白蛋白的吸附量均明显降低，且降低的程度与表面修饰的聚合物浓度有关。因此该系列聚合物可根据材料表面所带电荷的不同，吸附具有不同等电点的聚合物，因而起到很好的阳离子表面修饰作用。
Poly(amino acid)s have been extensively studied in biomedical applications,due to their unique regular secondary structures, rigid backbone, biocompatibility,biodegradability and various side groups for further functionalization. Most ofpolypeptides reported so far were prepared by ring-opening polymerization of aminoacid N-carboxyanhydrides (NCAs). However, the NCA approach has a costdisadvantage and a production problem because the pendant reactive groups carriedby the amino acids need to be protected prior to polymerization and deprotectedunder harsh conditions after polymerization to give the functional side groups. Poly(α, β-L-aspartic acid)(α, β-L-PAsp) can be synthesized by thermal polycondensationof L-aspartic acid (L-Asp), which is easily controlled and not costly. It would be agood candidate for preparing polypeptide derivatives.
In this thesis, Poly (amino acid)-based amphiphilic copolymer was utilized tofabricate a better micellar drug delivery system (DDS) with improved compatibilityand sustain release of Doxorubicin (DOX). First, Poly (ethylene glycol) monomethylether (MPEG) and DOX were conjugated onto polyasparihyazide, prepared via thereaction of poly (succinimide)(PSI) with hydrazine, to afford an amphiphilicpolymer [PEG-hyd-P (AHy-hyd-DOX)] with acid-liable hydrazone bonds. The DOX,chemically conjugated to the water-soluble polymer of the PAHy throughpH-sensitive hydrazone bond, was designed to supply hydrophobic segments andimprove the compatibility between the core and physically entrapped DOXmolecules. PEG segments grafted to the polymer via hydrazone bond was designedto prolong its lifetime in blood circulation. Free DOX molecules could be entrappedinto the nanoparticles of such an amphiphilic polymer via-interaction betweenthe conjugated and free DOX molecules to obtain a drug delivery system with highDOX load. The drug loading capacity, drug release behavior, and morphology of themicelles were investigated. The micelles’ biological activity was evaluated in vitro.Results showed that drug loading capacity was intensively augmented by adjusting the feed ratio, and the maximum loading capacity was as high as38%. Besides, theDOX-loaded system exhibited a pH-dependent drug release profile in vitro. Thecumulative release of DOX was much faster at pH5.0than that of the release at pH7.4. The DOX-loaded system kept highly antitumor activity for a long time,compared with free DOX. This easy-prepared DDS, with features ofbiocompatibility, biodegradability, high loading capacity and responsiveness to pH,was a promising candidate for the DOX delivery and controlled release.
In order to accelerate the rate of DOX release, a facile micelle-formingcopolymer-drug conjugate mPEG/IM-g-(PAHy-DOX) were reported. The DOX,chemically conjugated to the pH-responsive poly (amino acid)-based amphiphilicgraft polymer mPEG/IM-g-PAHy by hydrozone bonds, was designed to have a fasterrelease rate due to the presence of pH-sensitive group of imidazole. The drug loading,drug release, and morphology of the micelles were investigated. Compared with theamphiphilic polymer [PEG-hyd-P (AHy-hyd-DOX)], DOX-loaded system reportedhere has obviously enhanced pH-sensitivity and superior drug release behaviors, atpH5.0, the cumulative release of DOX from mPEG/IM-g-(PAHy-DOX)was muchfaster than that of the release from [PEG-hyd-P (AHy-hyd-DOX)].
An injectable poly (α,β-L-aspartic acid)-based hydrogel via hydrazonecrosslinking strategy was also studied in this thesis. The gelation occurs underphysiological conditions immediately upon mixing of the two aqueous poly(α,β-L-aspartic acid) derivatives specifically derivatized through hydrazone linkageswith aldehyde (PAPDAL) and hydrazide (PAHy) functional groups, respectively,without addition of crosslinker or catalyst. The fast gelation provides this systemwith injectable property. PAsp hydrogels were synthesized in PBS solution andcharacterized by different methods including gel content and swelling, Fouriertransformed infrared spectra, in vitro degradation and biocompatibility experiments.A scanning electron microscope viewed the interior morphology of gel whoseporous three-dimensional structure enabled it to efficiently encapsulate the drugs.Sustained and stable DOX release from the PAsp hydrogel was observed during invitro delivery experiments and exhibited its potentially high application prospect inthe field of protein drug delivery.
In addition, a novel zwitterionic polypeptide derivative, denoted as His-PAsp/PAsp,has been successfully synthesized by amidation of Poly (α, β-L-aspartic acid) withL-histidine methyl ester. Turbidity, zeta potential and1H NMR measurements wereused to study the aggregation behaviors of His-PAsp/PAsp under different pH values.The modified polypeptide derivative composed of certain negatively and positivelycharged residues randomly, exhibiting an isoelectric point (IEP) and bearing oppositecharges at pH values far high or below the isoelectric point. Silicon wafer, as a modelsubstrate material, was then coated with zwitterionic polypeptide. The amount ofprotein adsorbed to the coated surface could be controlled, depending on the dose ofthe polypeptide. Since its good biodegradability and superior anti-protein-foulingproperty, this pH-responsive zwitterionic polypeptide is a promising candidate forsurface modification in many biomedical applications, including medical implants,drug delivery carriers, and biosensors.
A series of zwitterionic dimethyl aminopropyl amine-grafted poly(α, β-L-asparticacid)s (DMAP-PASP) with pH-dependent charge profiles, were synthesized bysubsequent aminolysis polysuccinimide with3-dimethyl aminopropyl amine andalkali. The zwitterionic polypeptides had an IEP, which could be easily tuned frompH3.8to9.5and showed opposite charges below and above the IEP. Because of theflexibility of controlling pH dependence, it is expected that zwitterionicpolyaspartamide would have a number of biomedical applications, where the abilityto respond to delicate pH changes is required. The zwitterionic polypeptide was ableto inhibit the protein adsorption to the anionic surface at physiological pH. Theseresults warrant further exploration of zwitterionic polypeptides as a stealth coatingfor tumor-targeted nanocarriers to overcome the current limitation of PEG.
聚氨基酸类高分子材料因其良好的生物相容性、生物可吸收性及化学结构匹配性，在生物医用高分子领域有着无法比拟的优点和广泛的应用前景。特别是聚天冬氨酸，具有合成简单，成本较低，良好的生物相容性、生物降解性和可吸收性，易于功能化修饰等诸多优点。且在体内能够被逐渐吸收，其代谢产物对人体无毒，因而不会对周围组织、肝肾、血红细胞等产生毒副作用。因此聚天冬氨酸及其衍生物，被广泛用于药物载体的制备研究。关于聚天冬氨酸类载体已有很多报道，但是大部分的聚合物是通过N-羧酸酐（NCA）开环聚合方法合成得到聚(α-L-天冬氨酸)，这种方法制备的聚合物结构清晰明确，但合成步骤比较复杂，材料成本也相对提高。且一般认为聚-氨基酸二级结构过于规整，链段柔韧性差，不利于药物的扩散和释放。因此需要继续探索更为简便易行的可以实现肿瘤的特异性识别或富集或释放的响应性化学结构。本实验室以聚(α,β-L-天冬酰胺)为基本材料，设计具有环境刺激响应性能的生物降解高分子材料，并对其应用进行探索研究。
1）利用酸敏感的腙键将亲水的聚乙二醇和疏水性阿霉素键DOX合到聚天冬酰胺主链上，使得聚合物具有两亲性，再利用侧链键合的阿霉素与剩余游离阿霉素之间的疏水相互作用及-叠合作用将更多的阿霉素物理包埋到胶束内核。研究表明，通过调整DOX/Polymer的投料比，可以有效提高DOX的载药量，最高可达38%。该系列的纳米粒子稳定性好，体外实验表明，载有阿霉素的纳米粒子对阿霉素的释放具有良好的pH响应性。细胞结果表明载有阿霉素的纳米粒子保持了和自由阿霉素盐酸盐相近的药效。
2）以3-氨丙基咪唑和水合肼为亲核试剂，进攻聚琥珀酰亚胺进行开环反应得到氨丙基咪唑接枝聚天冬酰胺IM-g-PAHy。再利用醛化聚乙二醇PEG-CHO与肼基之间高效的反应形成腙键，得到侧链具有pH响应性官能团的两亲性聚合物mPEG/IM-g-PAHy，然后再将DOX通过腙键连接到聚合物骨架上，成功制备了得到了具有核可溶胀性的pH响应性阿霉素载药体系mPEG/IM-g-(PAHy-DOX)载药纳米粒子，并对其进行pH响应性、胶束形貌及释放动力学研究。研究发现，mPEG/IM-g-(PAHy-DOX)载药纳米粒子具有很好pH响应性，在pH7.4条件下，仅有少量释放，而在pH5.0条件下，最大释放量明显增加，且随着咪唑含量的增加，DOX的释放速度和释放量具有很大增加。但值得指出的是，随着聚合物中咪唑接枝度的增加，体系载药量也会随之降低。
3）生理条件下，利用腙键化学交联聚（α,β-L-天冬氨酸）衍生物原位制备水凝胶，成胶时间快，不需要加入任何小分子催化剂或交联剂。通过扫描电镜观察，水凝胶的内部均可以观察到致密、连贯的网络孔状结构。在模拟条件（pH=7.4和5.0，37℃）下，对聚（α,β-L-天冬氨酸）衍生物水凝胶进行降解行为研究发现，随着时间的推移水凝胶质量明显降低，28天降解35%-45%，说明该水凝胶具有很好的降解性能。以亲水性盐酸阿霉素为模型药物，研究了药物在该水凝胶中的装载和释放行为。在酸性环境pH时，阿霉素的释放速度的明显高于中性环境下的释放速度。根据Rigter-Peppas模型分析释放行为发现，在pH7.4生理条件下，阿霉素的释放遵循Fick扩机制，而在pH5.0酸性条件下，阿霉素在最初的释放过程中遵循无规扩散机制，即Fick扩散和高分子链的松弛协同作用结果。通过Hep G2细胞在水凝胶上的生长情况发现，该水凝胶支架有利于细胞的生长增殖。
4）设计了以-天冬氨酸为基本材料，对其聚合物侧链进行改性，制备了具有两性离子特性的聚氨基酸，作为具有pH敏感性的表面抗蛋白非特异性吸附材料，并对聚氨基酸的性质及等电点对抗蛋白质非特异性吸附能力的影响进行了系统的研究。
通过缩合反应制备得到的侧链部分接枝组氨酸HIS的聚（α,β-L-天冬氨酸）HIS-PAsp/PAsp，通过透过率、表面电势、酸碱滴定测试，证明其具有典型的两性离子特征。将其应用到无污染表面试验中可以看出，经静电吸附将HIS-PAsp/PAsp聚合物修饰到表面材料后纤维蛋白原的吸附量明显降低，且降低的程度与表面修饰的聚合物浓度有关。该材料有望成为一种很好的阳离子表面修饰材料。
通过氨基基团对聚琥珀酰亚胺（PSI）的开环反应引入弱碱性基团是一种效率高，条件可控的聚氨基酸衍生物制备方法。试验中制备了一系列具有不同等电点的两性离子叔胺化聚（α,β-L-天冬氨酸）DMPA-PAsp/Pasp。通过吸附试验证明，经静电吸附将不同等电点聚合物DMPA-PAsp/PAsp修饰到表面材料后对纤维蛋白原和白蛋白的吸附量均明显降低，且降低的程度与表面修饰的聚合物浓度有关。因此该系列聚合物可根据材料表面所带电荷的不同，吸附具有不同等电点的聚合物，因而起到很好的阳离子表面修饰作用。
Poly(amino acid)s have been extensively studied in biomedical applications,due to their unique regular secondary structures, rigid backbone, biocompatibility,biodegradability and various side groups for further functionalization. Most ofpolypeptides reported so far were prepared by ring-opening polymerization of aminoacid N-carboxyanhydrides (NCAs). However, the NCA approach has a costdisadvantage and a production problem because the pendant reactive groups carriedby the amino acids need to be protected prior to polymerization and deprotectedunder harsh conditions after polymerization to give the functional side groups. Poly(α, β-L-aspartic acid)(α, β-L-PAsp) can be synthesized by thermal polycondensationof L-aspartic acid (L-Asp), which is easily controlled and not costly. It would be agood candidate for preparing polypeptide derivatives.
In this thesis, Poly (amino acid)-based amphiphilic copolymer was utilized tofabricate a better micellar drug delivery system (DDS) with improved compatibilityand sustain release of Doxorubicin (DOX). First, Poly (ethylene glycol) monomethylether (MPEG) and DOX were conjugated onto polyasparihyazide, prepared via thereaction of poly (succinimide)(PSI) with hydrazine, to afford an amphiphilicpolymer [PEG-hyd-P (AHy-hyd-DOX)] with acid-liable hydrazone bonds. The DOX,chemically conjugated to the water-soluble polymer of the PAHy throughpH-sensitive hydrazone bond, was designed to supply hydrophobic segments andimprove the compatibility between the core and physically entrapped DOXmolecules. PEG segments grafted to the polymer via hydrazone bond was designedto prolong its lifetime in blood circulation. Free DOX molecules could be entrappedinto the nanoparticles of such an amphiphilic polymer via-interaction betweenthe conjugated and free DOX molecules to obtain a drug delivery system with highDOX load. The drug loading capacity, drug release behavior, and morphology of themicelles were investigated. The micelles’ biological activity was evaluated in vitro.Results showed that drug loading capacity was intensively augmented by adjusting the feed ratio, and the maximum loading capacity was as high as38%. Besides, theDOX-loaded system exhibited a pH-dependent drug release profile in vitro. Thecumulative release of DOX was much faster at pH5.0than that of the release at pH7.4. The DOX-loaded system kept highly antitumor activity for a long time,compared with free DOX. This easy-prepared DDS, with features ofbiocompatibility, biodegradability, high loading capacity and responsiveness to pH,was a promising candidate for the DOX delivery and controlled release.
In order to accelerate the rate of DOX release, a facile micelle-formingcopolymer-drug conjugate mPEG/IM-g-(PAHy-DOX) were reported. The DOX,chemically conjugated to the pH-responsive poly (amino acid)-based amphiphilicgraft polymer mPEG/IM-g-PAHy by hydrozone bonds, was designed to have a fasterrelease rate due to the presence of pH-sensitive group of imidazole. The drug loading,drug release, and morphology of the micelles were investigated. Compared with theamphiphilic polymer [PEG-hyd-P (AHy-hyd-DOX)], DOX-loaded system reportedhere has obviously enhanced pH-sensitivity and superior drug release behaviors, atpH5.0, the cumulative release of DOX from mPEG/IM-g-(PAHy-DOX)was muchfaster than that of the release from [PEG-hyd-P (AHy-hyd-DOX)].
An injectable poly (α,β-L-aspartic acid)-based hydrogel via hydrazonecrosslinking strategy was also studied in this thesis. The gelation occurs underphysiological conditions immediately upon mixing of the two aqueous poly(α,β-L-aspartic acid) derivatives specifically derivatized through hydrazone linkageswith aldehyde (PAPDAL) and hydrazide (PAHy) functional groups, respectively,without addition of crosslinker or catalyst. The fast gelation provides this systemwith injectable property. PAsp hydrogels were synthesized in PBS solution andcharacterized by different methods including gel content and swelling, Fouriertransformed infrared spectra, in vitro degradation and biocompatibility experiments.A scanning electron microscope viewed the interior morphology of gel whoseporous three-dimensional structure enabled it to efficiently encapsulate the drugs.Sustained and stable DOX release from the PAsp hydrogel was observed during invitro delivery experiments and exhibited its potentially high application prospect inthe field of protein drug delivery.
In addition, a novel zwitterionic polypeptide derivative, denoted as His-PAsp/PAsp,has been successfully synthesized by amidation of Poly (α, β-L-aspartic acid) withL-histidine methyl ester. Turbidity, zeta potential and1H NMR measurements wereused to study the aggregation behaviors of His-PAsp/PAsp under different pH values.The modified polypeptide derivative composed of certain negatively and positivelycharged residues randomly, exhibiting an isoelectric point (IEP) and bearing oppositecharges at pH values far high or below the isoelectric point. Silicon wafer, as a modelsubstrate material, was then coated with zwitterionic polypeptide. The amount ofprotein adsorbed to the coated surface could be controlled, depending on the dose ofthe polypeptide. Since its good biodegradability and superior anti-protein-foulingproperty, this pH-responsive zwitterionic polypeptide is a promising candidate forsurface modification in many biomedical applications, including medical implants,drug delivery carriers, and biosensors.
A series of zwitterionic dimethyl aminopropyl amine-grafted poly(α, β-L-asparticacid)s (DMAP-PASP) with pH-dependent charge profiles, were synthesized bysubsequent aminolysis polysuccinimide with3-dimethyl aminopropyl amine andalkali. The zwitterionic polypeptides had an IEP, which could be easily tuned frompH3.8to9.5and showed opposite charges below and above the IEP. Because of theflexibility of controlling pH dependence, it is expected that zwitterionicpolyaspartamide would have a number of biomedical applications, where the abilityto respond to delicate pH changes is required. The zwitterionic polypeptide was ableto inhibit the protein adsorption to the anionic surface at physiological pH. Theseresults warrant further exploration of zwitterionic polypeptides as a stealth coatingfor tumor-targeted nanocarriers to overcome the current limitation of PEG.
引文
[1] J. V. Gonzalez-Aramundiz, M. V. Lozano, A. Sousa-Herves, et al, Polypeptides andpolyaminoacids in drug delivery. Expert Opin Drug Del,2012,9(2):183-201
[2] M. L. Rogers, R. A. Rush, Non-viral gene therapy for neurological diseases, with an emphasison targeted gene delivery. J Control Release,2012,157(2):183-189
[3] M. J. Tiera, Q. Shi, F. M. Winnik, et al, Polycation-Based Gene Therapy: Current Knowledgeand New Perspectives. Curr Gene Ther,2011,11(4):288-306
[4] N. J. Boylan, A. J. Kim, J. S. Suk, et al, Enhancement of airway gene transfer by DNAnanoparticles using a pH-responsive block copolymer of polyethylene glycol and poly-L-lysine.Biomaterials,2012,33(7):2361-2371
[5] J. Du, Y. Sun, Q. S. Shi, et al, Biodegradable Nanoparticles of mPEG-PLGA-PLL TriblockCopolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing. Int JMol Sci,2012,13(1):516-533
[6] K. Itaka, K. Yamauchi, A. Harada, et al, Polyion complex micelles from plasmid DNA andpoly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system:physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials,2003,24(24):4495-4506
[7] Y. C. Huang, Y. S. Yang, T. Y. Lai, et al, Lysine-block-tyrosine block copolypeptides:Self-assembly, cross-linking, and conjugation of targeted ligand for drug encapsulation. Polymer,2012,53(4):913-922
[8] D. W. Pack, D. Putnam, R. Langer, Design of imidazole-containing endosomolyticbiopolymers for gene delivery. Biotechnol Bioeng,2000,67(2):217-223
[9] C. Pichon, C. Goncalves, P. Midoux, Histidine-rich peptides and polymers for nucleic acidsdelivery. Adv Drug Deliver Rev,2001,53(1):75-94
[10] I. K. Park, K. Singha, R. B. Arote, et al, pH-Responsive Polymers as Gene Carriers.Macromol Rapid Comm,2010,31(13):1122-1133
[11] S. B. Wang, F. H. Xu, H. S. He, et al, Novel alginate-poly(L-histidine) microcapsules as drugcarriers: In vitro protein release and short term stability. Macromol Biosci,2005,5(5):408-414
[12] E. S. Lee, K. T. Oh, D. Kim, et al, Tumor pH-responsive flower-like micelles of poly(L-lacticacid)-b-poly (ethylene glycol)-b-poly(L-histidine). J Control Release,2007,123(1):19-26
[13] J. Rodriguez-Hernandez, S. Lecommandoux, Reversible inside-out micellization ofpH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. J Am ChemSoc,2005,127(7):2026-2027
[14] T. Thambi, H. Y. Yoon, K. Kim, et al, Bioreducible Block Copolymers Based onPoly(Ethylene Glycol) and Poly(gamma-Benzyl L-Glutamate) for Intracellular Delivery ofCamptothecin. Bioconjugate Chem,2011,22(10):1924-1931
[15] C. Sanson, C. Schatz, J. F. Le Meins, et al, A simple method to achieve high doxorubicinloading in biodegradable polymersomes. J Control Release,2010,147(3):428-435
[16] Y. Wang, Y. N. Wang, G. L. Wu, et al, pH-Responsive Self-Assembly and conformationaltransition of partially propyl-esterified poly(alpha,beta-L-aspartic acid) as amphiphilicbiodegradable polyanion. Colloid Surface B,2009,68(1):13-19
[17] G. L. Zhang, J. B. Ma, Y. H. Li, et al, Synthesis and characterization ofpoly(L-alanine)-block-poly(ethylene glycol) monomethyl ether as amphiphilic biodegradableco-polymers. J Biomat Sci-Polym E,2003,14(12):1389-1400
[18] S. F. Yu, X. Gu, G. L. Wu, et al, Preparation and pH-Sensitive Drug Delivery Study ofmPEG-poly(Imidazole Propyl-Asparagine)-poly(L-Alanine). Acta Chim Sinica,2012,70(2):177-182
[19] H. R. Kricheldorf, Polypeptides and100years of chemistry of alpha-amino acidN-carboxyanhydrides. Angew Chem Int Edit,2006,45(35):5752-5784
[20] Schwmborn M, Degradation of polyaspartamides in vivo. Polym Degrad Stab,1998,59:39-50
[21]杨直, alpha,beta-聚[(N-羟丙基/氨乙基)-DL-天冬酰胺-CO-L-赖氨酸]:作为潜在的非病毒性基因载体的研究.浙江大学硕士毕业论文,2003
[22] H. Shinoda, Y. Asou, A. Suetsugu, et al, Synthesis and characterization of amphiphilicbiodegradable copolymer, poly(aspartic acid-co-lactic acid). Macromol Biosci,2003,3(1):34-43
[23] R. R. Ye, Z. Y. Wang, Q. F. Wang, et al, Synthesis of Biodegradable Material Poly(lacticacid-co-aspartic acid) via Direct Melt Polycondensation and Its Characterization. J Appl PolymSci,2011,121(6):3662-3668
[24] N. Nishiyama, K. Kataoka, Current state, achievements, and future prospects of polymericmicelles as nanocarriers for drug and gene delivery. Pharmacol Therapeut,2006,112(3):630-648
[25] M. Kumagai, Y. Imai, T. Nakamura, et al, Iron hydroxide nanoparticles coated withpoly(ethylene glycol)-poly(aspartic acid) block copolymer as novel magnetic resonance contrastagents for in vivo cancer imaging. Colloid Surface B,2007,56(1-2):174-181
[26] Y. Bae, K. Kataoka, Intelligent polymeric micelles from functional poly(ethyleneglycol)-poly(amino acid) block copolymers. Adv Drug Deliver Rev,2009,61(10):768-784
[27] K. Itaka, T. Ishii, Y. Hasegawa, et al, Biodegradable polyamino acid-based polycations assafe and effective gene carrier minimizing cumulative toxicity. Biomaterials,2010,31(13):3707-3714
[28] T. C. Lai, Y. Bae, T. Yoshida, et al, pH-Sensitive Multi-PEGylated Block Copolymer as aBioresponsive pDNA Delivery Vector. Pharm Res-Dordr,2010,27(11):2260-2273
[29] M. Oba, K. Miyata, K. Osada, et al, Polyplex micelles prepared from omega-cholesterylPEG-polycation block copolymers for systemic gene delivery. Biomaterials,2011,32(2):652-663
[30] G. Antoni, P. Neri, F. Benvenuti, et al, Synthesis of α, β-poly［(2-hydroxyethyl)-DL-aspartamide], a new plasma. J Med Chem,1973,16:893-904
[31]王勇;王亦农;伍国琳等,聚(α,β-L-天冬氨酸丁酯)的合成及水解降解行为研究.离子交换与吸附,2011,27:10-17
[32] M. Fresta, G. Cavallaro, G. Giammona, et al, Preparation and characterization ofpolyethyl-2-cyanoacrylate nanocapsules containing antiepileptic drugs. Biomaterials,1996,17(8):751-758
[33] G. Giammona, V. Tomarchio, G. Pitarresi, et al, Acryloylated alpha,beta-poly(N,hydroxyethyl)-DL-aspartamide and alpha,beta-polyasparthydrazide. Synthesis,characterization and radiation formation of polymeric networks. Colloid&Polymer Science,1997,275(1)
[34] T. Coviello, Y. Yuguchi, K. Kajiwara, et al, Conformational analysis ofalpha,beta-poly(N-hydroxyethyl)-dl-aspartamide (PHEA) and alpha,beta-polyasparthydrazide(PAHy) polymers in aqueous solution. Polymer,1998,39(17):4159-4164
[35] G. Giammona, G. Cavallaro, G. Fontana, et al, Coupling of the antiviral agent zidovudine topolyaspartamide and in vitro drug release studies. J Control Release,1998,54(3):321-331
[36] G. Giammona, G. Pitarresi, G. Cavallaro, et al, New biodegradable hydrogels based on aphotocrosslinkable modified polyaspartamide: synthesis and characterization. Biochimica EtBiophysica Acta-General Subjects,1999,1428(1):29-38
[37] R. Mendichi, G. Giammona, G. Cavallaro, et al, Molecular characterization ofalpha,beta-poly(asparthylhydrazide) a new synthetic polymer for biomedical applications.Polymer,1999,40(25):7109-7116
[38] G. Giammona, G. Cavallaro, G. Pitarresi, et al, Cationic copolymers ofalpha,beta-poly-(N-2-hydroxyethyl)-DL-aspartamide (PHEA) andalpha,beta-polyasparthylhydrazide (PAHy): synthesis and characterization. Polymer International,2000,49(1):93-98
[39] P. Caliceti, S. M. Quarta, F. M. Veronese, et al, Synthesis and biopharmaceuticalcharacterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers. BiochimicaEt Biophysica Acta-General Subjects,2001,1528(2-3):177-186
[40] R. Muzzalupo, F. Iemma, N. Picci, et al, Novel water-swellable beads based on anacryloylated polyaspartamide. Colloid and Polymer Science,2001,279(7):688-695
[41] E. Pedone, G. Cavallaro, S. C. W. Richardson, et al,alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers(PAHy-GTA): novel polymers with potential for DNA delivery. J Control Release,2001,77(1-2):139-153
[42] G. Cavallaro, M. Licciardi, G. Giammona, et al, Poly(hydroxyethyl aspartamide) derivativesas colloidal drug carrier systems. J Control Release,2003,89(2):285-295
[43] R. Mendichi, A. G. Schieroni, G. Cavallaro, et al, Molecular characterization ofalpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide derivatives as potential self-assemblingcopolymers forming polymeric micelles. Polymer,2003,44(17):4871-4879
[44] G. Cavallaro, M. Licciardi, P. Caliceti, et al, Synthesis, physico-chemical and biologicalcharacterization of a paclitaxel macromolecular prodrug. European Journal of Pharmaceutics andBiopharmaceutics,2004,58(1):151-159
[45] G. Cavallaro, L. Maniscalco, P. Caliceti, et al, Glycosilated macromolecular conjugates ofantiviral drugs with a polyaspartamide. Journal of Drug Targeting,2004,12(9-10):593-605
[46] G. Cavallaro, L. Maniscalco, G. Giammona, et al, Chemical conjugation of dexamethasone toa polyaspartamide and in vitro evaluation studies. Journal of Drug Delivery Science andTechnology,2004,14(5):373-381
[47] G. Cavallaro, L. Maniscalco, M. Licciardi, et al, Tamoxifen-loaded polymeric micelles:Preparation, physico-chemical characterization and in vitro evaluation studies. Macromol Biosci,2004,4(11):1028-1038
[48] E. F. Craparo, G. Cavallaro, M. L. Bondi, et al, Preparation of polymeric nanoparticles byphoto-crosslinking of an acryloylated polyaspartamide in w/o microemulsion. MacromolecularChemistry and Physics,2004,205(14):1955-1964
[49] G. Pitarresi, P. Pierro, G. Tripodo, et al, Drug delivery from mucoadhesive disks based on aphoto-cross-linkable polyaspartamide derivative. Journal of Drug Delivery Science andTechnology,2005,15(5):377-382
[50] E. F. Craparo, G. Cavallaro, M. L. Bondi, et al, PEGylated nanoparticles based on apolyaspartamide. Preparation, physico-chemical characterization, and intracellular uptake.Biomacromolecules,2006,7(11):3083-3092
[51] G. Giammona, G. Cavallaro, L. Maniscalco, et al, Synthesis and characterisation of novelchemical conjugates based on alpha,beta-polyaspartylhydrazide and beta-cyclodextrins. EuropeanPolymer Journal,2006,42(10):2715-2729
[52] G. Giammona, M. Licciardi, M. Campisi, et al, Synthesis and characterization ofpolyaminoacidic polycations for gene delivery. Biomaterials,2006,27(9)
[53] M. L. T. Liveri, G. Cavallaro, G. Giammona, et al, Amphiphilic derivatives of apolyaspartamide: their aggregation and solubilization ability. Colloids and Surfaces A(Physicochemical and Engineering Aspects),2006,289(1-3)
[54] G. Cavallaro, M. Licciardi, S. Scire, et al, New pegylated polyaspartamide-based polyplexesas gene delivery vectors. Nanomedicine,2010,5(2):243-258
[55] Y. Fernandez, E. Mottini, L. Pasotti, et al, Multicomponent polymeric micelles based onpolyaspartamide as tunable fluorescent pH-window biosensors. Biosensors&Bioelectronics,2010,26(1):29-35
[56] M. Licciardi, G. Cavallaro, M. D. Stefano, et al, New self-assembling polyaspartylhydrazidecopolymer micelles for anticancer drug delivery. International Journal of Pharmaceutics,2010,396(1-2):219-228
[57] M. Licciardi, D. Paolino, C. Celia, et al, Folate-targeted supramolecular vesicular aggregatesbased on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs.Biomaterials,2010,31(28):7340-7354
[58] M. Licciardi, G. Cavallaro, M. D. Stefano, et al, Polyaspartamide-graft-PolymethacrylateNanoparticles for Doxorubicin Delivery. Macromol Biosci,2011,11(3):445-454
[59] M. C. Ognibene, F. Rocco, E. F. Craparo, et al, Biocompatible Micelles Based on SqualenePortions Linked to PEGylated Polyaspartamide as Potential Colloidal Drug Carriers. CurrentNanoscience,2011,7(5):747-756
[60] M. G. Sarpietro, G. Pitarresi, S. Ottimo, et al, Interaction between Drug LoadedPolyaspartamide-Polylactide-Polysorbate Based Micelles and Cell Membrane Models: ACalorimetric Study. Molecular Pharmaceutics,2011,8(3):642-650
[61] S. R. Yang, S. B. Kim, C. O. Joe, et al, Self-aggregates of oligoarginine-conjugatedpoly(amino acid) derivatives as a carrier for intracellular drug delivery. Biotechnol Lett,2005,27(14):977-982
[62] H. M. Yang, H. J. Lee, K. S. Jang, et al, Poly(amino acid)-coated iron oxide nanoparticles asultra-small magnetic resonance probes. J Mater Chem,2009,19(26):4566-4574
[63] B. Jung, C. Y. Baek, J. Y. Yang, et al, Anticancer therapeutic self-aggregates of sphingolipidmetabolite-grafted poly(amino acid)-derivative and their enhanced intracellular delivery. J IndEng Chem,2010,16(6):1011-1018
[64] H. W. Park, H. S. Jin, S. Y. Yang, et al, Tunable phase transition behaviors of pH-sensitivepolyaspartamides having various cationic pendant groups. Colloid and Polymer Science,2009,287(8):919-926
[65] K. Seo, J. D. Kim, D. Kim, pH-dependent self-assembling behavior of imidazole-containingpolyaspartamide derivatives. J Biomed Mater Res A,2009,90A(2):478-486
[66] K. Seo, D. Kim, pH-dependent hemolysis of biocompatible imidazole-graftedpolyaspartamide derivatives. Acta Biomater,2010,6(6):2157-2164
[67] S. Kim, J. H. Kim, D. Kim, pH sensitive swelling and releasing behavior of nano-gels basedon polyaspartamide graft copolymers. J Colloid Interf Sci,2011,356(1):100-106
[68] W. Lin, D. Kim, pH-Sensitive Micelles with Cross-Linked Cores Formed fromPolyaspartamide Derivatives for Drug Delivery. Langmuir,2011,27(19):12090-12097
[69] H. M. Yang, C. W. Park, M. A. Woo, et al, HER2/neu Antibody Conjugated Poly(aminoacid)-Coated Iron Oxide Nanoparticles for Breast Cancer MR Imaging. Biomacromolecules,2010,11(11):2866-2872
[70] H. M. Yang, B. C. Oh, J. H. Kim, et al, Multifunctional poly(aspartic acid) nanoparticlescontaining iron oxide nanocrystals and doxorubicin for simultaneous cancer diagnosis and therapy.Colloid Surface A,2011,391(1-3):208-215
[71] S. R. Yang, H. J. Lee, J. D. Kim, Histidine-conjugated poly(amino acid) derivatives for thenovel endosomolytic delivery carrier of doxorubicin. J Control Release,2006,114(1):60-68
[72] R. Duncan, The dawning era of polymer therapeutics. Nat Rev Drug Discov,2003,2(5):347-360
[73] F. Greco, M. J. Vicent, Combination therapy: Opportunities and challenges for polymer-drugconjugates as anticancer nanomedicines. Adv Drug Deliver Rev,2009,61(13):1203-1213
[74] Y. Bae, S. Fukushima, A. Harada, et al, Design of environment-sensitive supramolecularassemblies for intracellular drug delivery: Polymeric micelles that are responsive to intracellularpH change. Angew Chem Int Edit,2003,42(38):4640-4643
[75] Y. Bae, W. D. Jang, N. Nishiyama, et al, Multifunctional polymeric micelles withfolate-mediated cancer cell targeting and pH-triggered drug releasing properties for activeintracellular drug delivery. Molecular Biosystems,2005,1(3):242-250
[76] Y. Bae, N. Nishiyama, S. Fukushima, et al, Preparation and biological characterization ofpolymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumorpermeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy.Bioconjugate Chem,2005,16(1):122-130
[77] P. Bawa, V. Pillay, Y. E. Choonara, et al, Stimuli-responsive polymers and their applicationsin drug delivery. Biomedical Materials,2009,4(2)
[78] Y. Chan, T. Wong, F. Byrne, et al, Acid-labile core cross-linked micelles for pH-triggeredrelease of antitumor drugs. Biomacromolecules,2008,9(7):1826-1836
[79] F. Corbellini, R. M. A. Knegtel, P. D. J. Grootenhuis, et al, Water-soluble molecular capsules:Self-assembly and binding properties. Chemistry-a European Journal,2005,11(1):298-307
[80] S. R. Croy, G. S. Kwon, Polymeric micelles for drug delivery. Current Pharmaceutical Design,2006,12(36):4669-4684
[81] M. Das, S. Mardyani, W. C. W. Chan, et al, Biofunctionalized pH-responsive microgels forcancer cell targeting: Rational design. Advanced Materials,2006,18(1):80-83
[82] E. R. Gillies, J. M. J. Frechet, pH-responsive copolymer assemblies for controlled release ofdoxorubicin. Bioconjugate Chem,2005,16(2):361-368
[83] J. X. Gu, W. P. Cheng, J. G. Liu, et al, pH-triggered reversible "stealth" polycationic micelles.Biomacromolecules,2008,9(1):255-262
[84] R. Haag, Supramolecular drug-delivery systems based on polymeric core-shell architectures.Angew Chem Int Edit,2004,43(3):278-282
[85] R. Haag, F. Kratz, Polymer therapeutics: Concepts and applications. Angew Chem Int Edit,2006,45(8):1198-1215
[86] J. M. Hu, S. Y. Liu, Responsive Polymers for Detection and Sensing Applications: CurrentStatus and Future Developments. Macromolecules,2010,43(20):8315-8330
[87] E. S. Lee, Z. G. Gao, Y. H. Bae, Recent progress in tumor pH targeting nanotechnology. JControl Release,2008,132(3):164-170
[88] A. Mahmud, X. B. Xiong, H. M. Aliabadi, et al, Polymeric micelles for drug targeting.Journal of Drug Targeting,2007,15(9):553-584
[89] J. K. Oh, R. Drumright, D. J. Siegwart, et al, The development of microgels/nanogels fordrug delivery applications. Progress in Polymer Science,2008,33(4):448-477
[90] K. T. Oh, H. Q. Yin, E. S. Lee, et al, Polymeric nanovehicles for anticancer drugs withtriggering release mechanisms. J Mater Chem,2007,17(38):3987-4001
[91] M. Oishi, H. Hayashi, I. D. Michihiro, et al, Endosomal release and intracellular delivery ofanticancer drugs using pH-sensitive PEGylated nanogels. J Mater Chem,2007,17(35):3720-3725
[92] N. Rapoport, Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery.Progress in Polymer Science,2007,32(8-9):962-990
[93] C. J. F. Rijcken, O. Soga, W. E. Hennink, et al, Triggered destabilisation of polymericmicelles and vesicles by changing polymers polarity: An attractive tool for drug delivery. JControl Release,2007,120(3):131-148
[94] R. Tong, J. J. Cheng, Anticancer polymeric nanomedicines. Polymer Reviews,2007,47(3):345-381
[95] C. H. Wang, G. H. Hsiue, Polymeric micelles with a pH-responsive structure as intracellulardrug carriers. J Control Release,2005,108(1):140-149
[96] N. Wiradharma, Y. Zhang, S. Venkataraman, et al, Self-assembled polymer nanostructures fordelivery of anticancer therapeutics. Nano Today,2009,4(4):302-317
[97] Q. Yang, S. H. Wang, P. W. Fan, et al, pH-responsive carrier system based on carboxylic acidmodified mesoporous silica and polyelectrolyte for drug delivery. Chemistry of Materials,2005,17(24):5999-6003
[98] Z. Amoozgar, Y. Yeo, Recent advances in stealth coating of nanoparticle drug deliverysystems. Wiley Interdisciplinary Reviews-Nanomedicine and Nanobiotechnology,2012,4(2):219-233
[99] T. Kaasgaard, T. L. Andresen, Liposomal cancer therapy: exploiting tumor characteristics.Expert Opin Drug Del,2010,7(2):225-243
[100] C. Li, S. Wallace, Polymer-drug conjugates: Recent development in clinical oncology. AdvDrug Deliver Rev,2008,60(8):886-898
[101] W. B. Liechty, N. A. Peppas, Expert opinion: Responsive polymer nanoparticles in cancertherapy. European Journal of Pharmaceutics and Biopharmaceutics,2012,80(2):241-246
[102] W. W. Gao, J. M. Chan, O. C. Farokhzad, pH-Responsive Nanoparticles for Drug Delivery.Molecular Pharmaceutics,2010,7(6):1913-1920
[103] S. Asayama, H. Kato, H. Kawakami, et al, Carboxymethyl poly(L-histidine) as a newpH-sensitive polypeptide at endosomal/lysosomal pH. Polymers for Advanced Technologies,2007,18(4):329-333
[104] G. Mohajer, E. S. Lee, Y. H. Bae, Enhanced intercellular retention activity of novelpH-sensitive polymeric micelles in wild and multidrug resistant MCF-7cells. Pharm Res-Dordr,2007,24(9):1618-1627
[105] A. Taluja, Y. H. Bae, Role of a novel excipient poly(ethylene Glycol)-b-poly(L-histidine) inretention of physical stability of insulin in aqueous solutions. Pharm Res-Dordr,2007,24(8):1517-1526
[106] M. Casolaro, Y. Ito, T. Ishii, et al, Stimuli-responsive poly(ampholyte)s containingL-histidine residues: synthesis and protonation thermodynamics of methacrylic polymers in thefree and in the cross-linked gel forms. Express Polymer Letters,2008,2(3):165-183
[107] D. Kim, E. S. Lee, K. Park, et al, Doxorubicin Loaded pH-sensitive Micelle: AntitumoralEfficacy against Ovarian A2780/DOX(R) Tumor. Pharm Res-Dordr,2008,25(9):2074-2082
[108] E. S. Lee, Z. G. Gao, D. Kim, et al, Super pH-sensitive multifunctional polymeric micellefor tumor pH(e) specific TAT exposure and multidrug resistance. J Control Release,2008,129(3):228-236
[109] K. T. Oh, E. S. Lee, Cancer-associated pH-responsive tetracopolymeric micelles composedof poly(ethylene glycol)-b-poly(L-histidine)-b-poly(L-lactic acid)-b-poly(ethylene glycol).Polymers for Advanced Technologies,2008,19(12):1907-1913
[110] K. T. Oh, E. S. Lee, D. Kim, et al, L-Histidine-based pH-sensitive anticancer drug carriermicelle: Reconstitution and brief evaluation of its systemic toxicity. International Journal ofPharmaceutics,2008,358(1-2):177-183
[111] H. Q. Yin, E. S. Lee, D. Kim, et al, Physicochemical characteristics of pH-sensitivepoly(L-Histidine)-b-poly (ethylene glycol)/poly(L-Lactide)-b-poly(ethylene glycol) mixedmicelles. J Control Release,2008,126(2):130-138
[112] K. T. Oh, D. Kim, H. H. You, et al, pH-sensitive properties of surface charge-switchedmultifunctional polymeric micelle. International Journal of Pharmaceutics,2009,376(1-2):134-140
[113] H. Q. Yin, Y. H. Bae, Physicochemical aspects of doxorubicin-loaded pH-sensitivepolymeric micelle formulations from a mixture ofpoly(L-histidine)-b-poly(L-lactide)-b-poly(ethylene glycol). European Journal of Pharmaceuticsand Biopharmaceutics,2009,71(2):223-230
[114] P. Dutta, J. Dey, Drug solubilization by amino acid based polymeric nanoparticles:Characterization and biocompatibility studies. International Journal of Pharmaceutics,2011,421(2):353-363
[115] Z. G. Gao, L. Tian, J. Hu, et al, Prevention of metastasis in a4T1murine breast cancermodel by doxorubicin carried by folate conjugated pH sensitive polymeric micelles. J ControlRelease,2011,152(1):84-89
[116] R. Liu, D. Li, B. He, et al, Anti-tumor drug delivery of pH-sensitive poly(ethyleneglycol)-poly(L-histidine-)-poly(L-lactide) nanoparticles. J Control Release,2011,152(1):49-56
[117] F. X. Zhan, W. Chen, Z. J. Wang, et al, Acid-Activatable Prodrug Nanogels for EfficientIntracellular Doxorubicin Release. Biomacromolecules,2011,12(10):3612-3620
[118] T. Etrych, M. Jelinkova, B. Rihova, et al, New HPMA copolymers containing doxorubicinbound via pH-sensitive linkage: synthesis and preliminary in vitro and in vivo biologicalproperties. J Control Release,2001,73(1):89-102
[119] C. X. Ding, J. X. Gu, X. Z. Qu, et al, Preparation of Multifunctional Drug Carrier forTumor-Specific Uptake and Enhanced Intracellular Delivery through the Conjugation of WeakAcid Labile Linker. Bioconjugate Chem,2009,20(6):1163-1170
[120] E. R. Gillies and J. M. J. Fréchet, pH-Responsive Copolymer Assemblies for ControlledRelease of Doxorubicin. Bioconjugate Chem,2005,16(2):361-368
[121] R. P. Tang, W. H. Ji, D. Panus, et al, Block copolymer micelles with acid-labile ortho esterside-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells. JControl Release,2011,151(1):18-27
[122] H. Cabral, K. Kataoka, Multifunctional nanoassemblies of block copolymers for futurecancer therapy. Science and Technology of Advanced Materials,2010,11(1)
[123] Rong Tong, David A. Christian, Li Tang, et al, Nanopolymeric Therapeutics. Mrs Bulletin,2009,34(6):422-431
[124] M. Zhang, K. Kataoka, Nano-structured composites based on calcium phosphate for cellulardelivery of therapeutic and diagnostic agents. Nano Today,2009,4(6):508-517
[125] K. Osada, R. J. Christie, K. Kataoka, Polymeric micelles from poly(ethyleneglycol)-poly(amino acid) block copolymer for drug and gene delivery. Journal of the RoyalSociety Interface,2009,6:S325-S339
[126] R. Scherer, J. Kreuter, Influence of enzymes on the stability of poly butylcyanoacrylatenanoparticles. Int J Pharm,1994,101:165-176
[127]王成运;公彦宝;刘顺英等, α,β-聚[N-(丁二酸基)-L-天冬酰胺]的合成及其顺铂大分子药物的细胞毒性.高等化学学报,2008,29:1665-1670
[128] S. J. Lee, K. H. Min, H. J. Lee, et al, Ketal Cross-Linked Poly(ethylene glycol)-Poly(aminoacid)s Copolymer Micelles for Efficient Intracellular Delivery of Doxorubicin.Biomacromolecules,2011,12(4):1224-1233
[129] C. L. Wu, H. He, H. J. Gao, et al, Synthesis of Fe(3)O(4)@SiO(2)@polymer nanoparticlesfor controlled drug release. Sci China Chem,2010,53(3):514-518
[130] Y. K. Xue, X. X. Tang, J. Huang, et al, Anti-tumor efficacy of polymer-platinum(II)complex micelles fabricated from folate conjugated PEG-graft-alpha,beta-poly [(N-aminoacidyl)-aspartamide] and cis-dichlorodiammine platinum(II) in tumor-bearing mice. ColloidSurface B,2011,85(2):280-288
[131] M. Yokoyama, S. Fukushima, R. Uehara, et al, Characterization of physical entrapment andchemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery toa solid tumor. J Control Release,1998,50(1-3):79-92
[132] J. Cabral, S. C. Moratti, Hydrogels for biomedical applications. Future Med Chem,2011,3(15):1877-1888
[133] J. Jagur-Grodzinski, Polymeric gels and hydrogels for biomedical and pharmaceuticalapplications. Polymers for Advanced Technologies,2010,21(1):27-47
[134] I. Tomatsu, K. Peng, A. Kros, Photoresponsive hydrogels for biomedical applications. AdvDrug Deliver Rev,2011,63(14-15):1257-1266
[135] F. Chiellini, R. Bizzarri, C. K. Ober, et al, Patterning of polymeric hydrogels for biomedicalapplications. Macromol Rapid Comm,2001,22(15):1284-1287
[136] L. H. Zhou, G. Y. Huang, S. Q. Wang, et al, Advances in cell-based biosensors usingthree-dimensional cell-encapsulating hydrogels. Biotechnol J,2011,6(12):1466-1476
[137] A. Wadee, V. Pillay, Y. E. Choonara, et al, Recent advances in the design of drug-loadedpolymeric implants for the treatment of solid tumors. Expert Opin Drug Del,2011,8(10):1323-1340
[138] P. BARTL O. WICHTERLE, M. ROSENBERG, Water-Soluble Methacrylates asEmbedding Media for Preparation of Ultra-Thin Sections. Nature,1960,186:494-495
[139] D. LiM O. WICHTERLE, Hydrophilic Gels for Biological Use. Nature,1960,185:117-118
[140] W. A. Laftah, S. Hashim, A. N. Ibrahim, Polymer Hydrogels: A Review. Polym-PlastTechnol,2011,50(14):1475-1486
[141] S. N. Pawar, K. J. Edgar, Alginate derivatization: A review of chemistry, properties andapplications. Biomaterials,2012,33(11):3279-3305
[142] X. Xu, A. K. Jha, D. A. Harrington, et al, Hyaluronic acid-based hydrogels: from a naturalpolysaccharide to complex networks. Soft Matter,2012,8(12):3280-3294
[143] H. T. Ta, C. R. Dass, D. E. Dunstan, Injectable chitosan hydrogels for localised cancertherapy. J Control Release,2008,126(3):205-216
[144] C. W. Zhao, X. L. Zhuang, P. He, et al, Synthesis of biodegradable thermo-andpH-responsive hydrogels for controlled drug release. Polymer,2009,50(18):4308-4316
[145] H. B. Zhang, C. Zhao, H. Cao, et al, Hyperbranched poly(amine-ester) based hydrogels forcontrolled multi-drug release in combination chemotherapy. Biomaterials,2010,31(20):5445-5454
[146] D. A. Ossipov, S. Piskounova, J. Hilborn, Poly(vinyl alcohol) cross-linkers for in vivoinjectable hydrogels. Macromolecules,2008,41(11):3971-3982
[147] J. H. Ahn, Y. S. Jeon, D. J. Chung, et al, Preparation and Swelling Behavior ofStimuli-responsive PHEMA Hybrid Gels. Polym-Korea,2011,35(1):94-98
[148] D. D. Diaz, D. Kuhbeck, R. J. Koopmans, Stimuli-responsive gels as reaction vessels andreusable catalysts. Chem Soc Rev,2011,40(1):427-448
[149] T. Z. Grove, C. O. Osuji, J. D. Forster, et al, Stimuli-Responsive Smart Gels Realized viaModular Protein Design. J Am Chem Soc,2010,132(40):14024-14026
[150] S. K. Ahn, R. M. Kasi, S. C. Kim, et al, Stimuli-responsive polymer gels. Soft Matter,2008,4(6):1151-1157
[151] M. Toda, F. Tanaka, Mechanically induced helicity in chiral stimuli-responsive gels.Macromolecules,2007,40(13):4703-4709
[152] W. G. Weng, J. B. Beck, A. M. Jamieson, et al, Understanding the mechanism of gelationand stimuli-responsive nature of a class of metallo-supramolecular gels. J Am Chem Soc,2006,128(35):11663-11672
[153] E. Marsano, E. Blanchi, S. Vicini, et al, Stimuli responsive gels based on interpenetratingnetwork of chitosan and poly(vinylpyrrolidone). Polymer,2005,46(5):1595-1600
[154] H. J. Kim, J. H. Lee, M. Lee, Stimuli-responsive gels from reversible coordination polymers.Angew Chem Int Edit,2005,44(36):5810-5814
[155] M. Burt, B. C. Dave, Use of stimuli-responsive organosilica sol-gels in detection andsensing.2004. Abstr Pap Am Chem S,2004,227:U492-U492
[156] B. C. Dave, M. S. Rao, Use of stimuli-responsive organosilica sol-gels in separation/releaseof molecules. Abstr Pap Am Chem S,2004,227:U891-U891
[157] E. Marsano, E. Bianchi, A. Viscardi, Stimuli responsive gels based on interpenetratingnetwork of hydroxy propylcellulose and poly (N-isopropylacrylamide). Polymer,2004,45(1):157-163
[158] Y. H. Ma, Y. Q. Tang, N. C. Billingham, et al, Synthesis of biocompatible,stimuli-responsive, physical gels based on ABA triblock copolymers. Biomacromolecules,2003,4(4):864-868
[159] H. Goto, H. Q. Zhang, E. Yashima, Chiral stimuli-responsive gels: Helicity induction inpoly(phenylacetylene) gels bearing a carboxyl group with chiral amines. J Am Chem Soc,2003,125(9):2516-2523
[160] K. Kulbaba, M. J. MacLachlan, C. E. B. Evans, et al, Stimuli-responsive gels based onring-opened polyferrocenes: Synthesis, characterization, and electrochemical studies of swellable,thermally cross-linked polyferrocenylsilanes. Acs Sym Ser,2003,833:175-188
[161] R. Deen, L. H. Gan, Studies of new piperazine based stimuli-responsive gels. Abstr Pap AmChem S,2001,222:U377-U377
[162] L. L. Zhao, L. J. Zhu, F. Y. Liu, et al, pH triggered injectable amphiphilic hydrogelcontaining doxorubicin and paclitaxel. International Journal of Pharmaceutics,2011,410(1-2):83-91
[163] S. H. Nezhadi, P. F. M. Choong, F. Lotfipour, et al, Gelatin-based delivery systems forcancer gene therapy. Journal of Drug Targeting,2009,17(10):731-738
[164] Y. J. Yin, Z. Y. Li, Y. B. Sun, et al, A preliminary study on chitosan/gelatin polyelectrolytecomplex formation.. J Mater Sci,2005,40(17):4649-4652
[165] M. J. Song, D. S. Lee, J. H. Ahn, et al, Dielectric behavior during sol-gel transition ofPEO-PPO-PEO triblock copolymer aqueous solution.. Polym Bull,2000,43(6):497-504
[166] A. Sosnik, D. Cohn, J. S. San Roman, et al, Crosslinkable PEO-PPO-PEO-based reversethermo-responsive gels as potentially injectable materials. J Biomat Sci-Polym E,2003,14(3):227-239
[167] K. P. Schneider, E. Wehrschuetz-Sigl, S. J. Eichhorn, et al, Bioresponsive systems based oncrosslinked polysaccharide hydrogels. Process Biochem,2012,47(2):305-311
[168] G. R. Hendrickson, L. A. Lyon, Bioresponsive hydrogels for sensing applications. SoftMatter,2009,5(1):29-35
[169] R. V. Ulijn, N. Bibi, V. Jayawarna, et al, Bioresponsive hydrogels. Mater Today,2007,10(4):40-48
[170] J. Kim, N. Singh, M. Serpe, et al, Towards the design of bioresponsive hydrogels. Abstr PapAm Chem S,2006,231
[171] D. A. Wang, C. G. Williams, F. Yang, et al, Bioresponsive phosphoester hydrogels for bonetissue engineering. Tissue Eng,2005,11(1-2):201-213
[172] B. R. Nayak, T. L. Lowe, Novel biodegradable-Co-bioresponsive hydrogels for drugdelivery. Abstr Pap Am Chem S,2003,225:U680-U680
[173] A. Matsumoto, K. Yamamoto, R. Yoshida, et al, A totally synthetic glucose responsive geloperating in physiological aqueous conditions. Chem Commun,2010,46(13):2203-2205
[174] R. V. Ulijn, Enzyme-responsive materials: a new class of smart biomaterials. J Mater Chem,2006,16(23):2217-2225
[175] B. Yurke, D. C. Lin, N. A. Langrana, Use of DNA nanodevices in modulating themechanical properties of polyacrylamide gels. Lect Notes Comput Sc,2006,3892:417-426
[176] Y. L. Li, J. Rodrigues, H. Tomas, Injectable and biodegradable hydrogels: gelation,biodegradation and biomedical applications. Chem Soc Rev,2012,41(6):2193-2221
[177] C. T. Huynh, M. K. Nguyen, D. S. Lee, Injectable Block Copolymer Hydrogels:Achievements and Future Challenges for Biomedical Applications. Macromolecules,2011,44(17):6629-6636
[178] D. Macaya, M. Spector, Injectable hydrogel materials for spinal cord regeneration: a review.Biomedical Materials,2012,7(1)
[179] T. Delair, In situ forming polysaccharide-based3D-hydrogels for cell delivery inregenerative medicine. Carbohyd Polym,2012,87(2):1013-1019
[180]曹辉，孙绍华，苏海佳等,聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展.化工进展,2009,28:1991-1994
[181] N. Akinori，T. Hiroaki，A. Masanobu, Superabsorbent polymer and process for producingsame.1995.
[182] V. Torma, T. Gyenes, Z. Szakacs, et al, A novel potentiometric method for the determinationof real crosslinking ratio of poly(aspartic acid) gels. Acta Biomater,2010,6(3):1186-1190
[183] Z. Varga, K. Molnar, V. Torma, et al, Kinetics of volume change of poly(succinimide) gelsduring hydrolysis and swelling. Phys Chem Chem Phys,2010,12(39):12670-12675
[184] T. Gyenes, V. Torma, M. Zrinyi, Swelling properties of aspartic acid-based hydrogels.Colloid Surface A,2008,319(1-3):154-158
[185] T. Gyenes, V. Torma, B. Gyarmati, et al, Synthesis and swelling properties of novelpH-sensitive poly(aspartic acid) gels. Acta Biomater,2008,4(3):733-744
[186] S. W. Yoon, D. J. Chung, J. H. Kim, Preparation and swelling behavior of biodegradablehydrogels based on alpha,beta-poly(N-2-hydroxyethyl-DL-aspartamide). J Appl Polym Sci,2003,90(13):3741-3746
[187] J. H. Kim, J. H. Lee, S. W. Yoon, Preparation and swelling behavior of biodegradablesuperabsorbent gels based on polyaspartic acid. J Ind Eng Chem,2002,8(2):138-142
[188] S. K. Min, S. H. Kim, J. H. Kim, Preparation and swelling behavior of biodegradablepoly(aspartic acid)-based hydrogel. J Ind Eng Chem,2000,6(4):276-279
[189] J. Yang, F. Wang, T. W. Tan, Degradation Behavior of Hydrogel Based on Cross linkedPoly(aspartic acid). J Appl Polym Sci,2010,117(1):178-185
[190] G. Giammona, B. Carlisia, G. Cavallaroa, G., et al, A new water-soluble synthetic polymer,α,β-polyasparthydrazide, as potential plasma expander and drug carrier. J Control Release,1994,29:63-72
[191] G. Pitarresi, F. S. Palumbo, G. Cavallaro, et al, Scaffolds based on hyaluronan crosslinkedwith a polyaminoacid: Novel candidates for tissue engineering application. J Biomed Mater Res A,2008,87A(3):770-779
[192] D. Mandracchia, G. Pitarresi, F. S. Palumbo, et al, PH-Sensitive hydrogel based on a novelphotocross-linkable copolymer. Biomacromolecules,2004,5(5):1973-1982
[193] J. H. Park, J. R. Moon, K. H. Hong, et al, Photo-crosslinked polyaspartamide hybrid gelcontaining thermo-responsive Pluronic triblock copolymer. J Polym Res,2011,18(2):273-278
[194] G. Spadaro， C. Dispenza， G. Giammona, Cytarabine release from α,β-poly(N-hydroxyethyl)-DL-aspartamide matrices cross-linked through γ-radiation. Biomaterials,1996,17:953-958
[195] V. Tomarchio, G. Giammona, G. Pitarresi, et al, Glycidyl methacrylate derivatization ofα,β-poly(N-hydroxyethyl)-dl-aspartamide and α,β-polyasparthydrazide. Polym Bull,1997,38:3315-3323
[196]刘姗,朱健婷,苏海佳, pH敏感型聚天冬氨酸水凝胶制备工艺的优化及其释药性能.材料导报：研究篇,2010,24:100-103
[197] G. Giammona, G. Pitarresi, G. Cavallaro, et al, pH-sensitive hydrogel based on apolyaspartamide derivative. Journal of Drug Delivery Science and Technology,2006,16(1):77-84
[198] G. Giammona, G. Pitarresi, E. F. Craparo, et al, New biodegradable hydrogels based on aphoto-cross-linkable polyaspartamide and poly(ethylene glycol) derivatives. Release studies of ananticancer drug. Colloid and Polymer Science,2001,279(8):771-783
[199] G. Giammona, G. Pitarresi, V. Tomarchio, et al, A hydrogel based on polyaspartamide:Characterization and evaluation of in-vivo biocompatibility and drug release in the rat. Journal ofPharmacy and Pharmacology,1997,49(11):1051-1056
[200]常宪智，于跃芹，田红杰等，聚天冬氨酸交联温敏性水凝胶的药物缓释性能.高分子材料科学与工程，2009，25:79-82
[201] S. Salmaso, R. Schrepfer, G. Cavallaro, et al, Supramolecular association of recombinanthuman growth hormone with hydrophobized polyhydroxyethylaspartamides. European Journal ofPharmaceutics and Biopharmaceutics,2008,68(3):656-666
[202]王健，刘振华，卓仁禧， α，β-聚-DL-天冬酰胺衍生物水凝胶的合成及其溶胀性能研究.高分子学报，1998,5:563-566
[203]吴军，陈强，李利等，可降解聚天冬氨酸水凝胶的制备与应用研究.材料导报，2005,19:126-128
[204] R. Zhang, Z. B. Huang, M. Y. Xue, et al, Detailed characterization of an injectablehyaluronic acid-polyaspartylhydrazide hydrogel for protein delivery. Carbohyd Polym,2011,85(4):717-725
[205] C. Sperling, M. Fischer, M. F. Maitz, et al, Blood coagulation on biomaterials requires thecombination of distinct activation processes. Biomaterials,2009,30(27):4447-4456
[206] P. Aggarwal, J. B. Hall, C. B. McLeland, et al, Nanoparticle interaction with plasmaproteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. AdvDrug Deliver Rev,2009,61(6):428-437
[207] B. Thierry, L. Zimmer, S. McNiven, et al, Electrostatic Self-Assembly of PEG Copolymersonto Porous Silica Nanoparticles. Langmuir,2008,24(15):8143-8150
[208] C. Rodriguez-Emmenegger, A. J ger, E. J ger, et al, Polymeric nanocapsules ultra stable incomplex biological media. Colloids and Surfaces B: Biointerfaces,2011,83(2):376-381
[209] C.B Geer, I.A Rus, S.T Lord, et al, Surface-dependent fibrinopeptide A accessibility tothrombin. Acta Biomater,2007,3(5):663
[210] I. Lynch, A. Salvati, K. A. Dawson, Protein-nanoparticle interactions: What does the cell see.Nat Nano,2009,4(9):546-547
[211] A. E. Nel, L. Madler, D. Velegol, et al, Understanding biophysicochemical interactions atthe nano-bio interface. Nature Materials,2009,8(7):543-557
[212] T. Ren, Y. Feng, H. Dong, et al, Sheddable Nanoparticles for Biomedical Application.Progress in Chemistry,2011,23(1):213-220
[213] B. Romberg, W. E. Hennink, G. Storm, Sheddable coatings for long-circulatingnanoparticles. Pharm Res-Dordr,2008,25(1):55-71
[214] M. Wang, M. Thanou, Targeting nanoparticles to cancer. Pharmacological Research,2010,62(2):90-99
[215] S. Zhang, Y. Shi, C. Huang, et al, Design of spectral reflective properties of the stealthcoating. Acta Physica Sinica,2007,56(9):5508-5512
[216] L. Y. Li, S. F. Chen, J. Zheng, et al, Protein adsorption on oligo(ethylene glycol)-terminatedalkanethiolate self-assembled monolayers: The molecular basis for nonfouling behavior. J PhysChem B,2005,109(7):2934-2941
[217] J. Zheng, L. Y. Li, H. K. Tsao, et al, Strong repulsive forces between protein and oligo(ethylene glycol) self-assembled monolayers: A molecular simulation study. Biophys J,2005,89(1):158-166
[218] D. E. Owens Iii, N. A. Peppas, Opsonization, biodistribution, and pharmacokinetics ofpolymeric nanoparticles. International Journal of Pharmaceutics,2006,307(1):93-102
[219] S. F. Chen, L. Y. Liu, S. Y. Jiang, Strong resistance of oligo(phosphorylcholine)self-assembled monolayers to protein adsorption. Langmuir,2006,22(6):2418-2421
[220] S. F. Chen, J. Zheng, L. Y. Li, et al, Strong resistance of phosphorylcholine self-assembledmonolayers to protein adsorption: Insights into nonfouling properties of zwitterionic materials. JAm Chem Soc,2005,127(41):14473-14478
[221] Y. He, J. Hower, S. F. Chen, et al, Molecular simulation studies of protein interactions withzwitterionic phosphorylcholine self-assembled monolayers in the presence of water. Langmuir,2008,24(18):10358-10364
[222] J. Ladd, Z. Zhang, S. Chen, et al, Zwitterionic polymers exhibiting high resistance tononspecific protein adsorption from human serum and plasma. Biomacromolecules,2008,9(5):1357-1361
[223] G. Cheng, Z. Zhang, S. F. Chen, et al, Inhibition of bacterial adhesion and biofilm formationon zwitterionic surfaces. Biomaterials,2007,28(29):4192-4199
[224] Z. Zhang, G. Cheng, L. R. Carr, et al, The hydrolysis of cationic polycarboxybetaine estersto zwitterionic polycarboxybetaines with controlled properties. Biomaterials,2008,29(36):4719-4725
[225] N. D. Brault, C. L. Gao, H. Xue, et al, Ultra-low fouling and functionalizable zwitterioniccoatings grafted onto SiO(2) via a biomimetic adhesive group for sensing and detection incomplex media. Biosensors&Bioelectronics,2010,25(10):2276-2282
[226] C. L. Gao, G. Z. Li, H. Xue, et al, Functionalizable and ultra-low fouling zwitterionicsurfaces via adhesive mussel mimetic linkages. Biomaterials,2010,31(7):1486-1492
[227] G. Z. Li, G. Cheng, H. Xue, et al, Ultra low fouling zwitterionic polymers with a biomimeticadhesive group. Biomaterials,2008,29(35):4592-4597
[228] W. Yang, L. Zhang, S. L. Wang, et al, Functionalizable and ultra stable nanoparticles coatedwith zwitterionic poly(carboxybetaine) in undiluted blood serum. Biomaterials,2009,30(29):5617-5621
[229] L. Zhang, H. Xue, C. L. Gao, et al, Imaging and cell targeting characteristics of magneticnanoparticles modified by a functionalizable zwitterionic polymer with adhesive3,4-dihydroxyphenyl-L-alanine linkages. Biomaterials,2010,31(25):6582-6588
[230] Z. Q. Cao, Q. M. Yu, H. Xue, et al, Nanoparticles for Drug Delivery Prepared fromAmphiphilic PLGA Zwitterionic Block Copolymers with Sharp Contrast in Polarity between TwoBlocks. Angew Chem Int Edit,2010,49(22):3771-3776
[231] J. Kopecek, P. Kopeckova, HPMA copolymers: Origins, early developments, present, andfuture. Adv Drug Deliver Rev,2010,62(2):122-149
[232] T. Lammers, V. Subr, K. Ulbrich, et al, Simultaneous delivery of doxorubicin andgemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials,2009,30(20):3466-3475
[233] J. M. Metselaar, P. Bruin, L. W. T. de Boer, et al, A novel family of L-amino acid-basedbiodegradable polymer-lipid conjugates for the development of long-circulating liposomes witheffective drug-targeting capacity. Bioconjugate Chem,2003,14(6):1156-1164
[234] B. Romberg, J. M. Metselaar, L. Baranyi, et al, Poly(amino acid)s: Promising enzymaticallydegradable stealth coatings for liposomes. International Journal of Pharmaceutics,2007,331(2):186-189
[235] B. Romberg, C. Oussoren, C. J. Snel, et al, Pharmacokinetics ofpoly(hydroxyethyl-L-asparagine)-coated liposomes is superior over that of PEG-coated liposomesat low lipid dose and upon repeated administration. Bba-Biomembranes,2007,1768(3):737-743
[236] S. F. Chen, Z. Q. Cao, S. Y. Jiang, Ultra-low fouling peptide surfaces derived from naturalamino acids. Biomaterials,2009,30(29):5892-5896
[237] B. Romberg, W. Hennink, G. Storm, Sheddable Coatings for Long-CirculatingNanoparticles. Pharm Res-Dordr,2008,25(1):55-71
[238] H. Hatakeyama, H. Akita, K. Kogure, et al, Development of a novel systemic gene deliverysystem for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Therapy,2006,14(1):68-77
[239] C. Clawson, L. Ton, S. Aryal, et al, Synthesis and Characterization of Lipid-Polymer HybridNanoparticles with pH-Triggered Poly(ethylene glycol) Shedding. Langmuir,2011,27(17):10556-10561
[240] A. Soderberg, B. Sahaf, A. Rosen, Thioredoxin reductase, a redox-active selenoprotein, issecreted by normal and neoplastic cells: Presence in human plasmal. Cancer Res,2000,60(8):2281-2289
[241] T. B. Ren, W. J. Xia, H. Q. Dong, et al, Sheddable micelles based on disulfide-linked hybridPEG-polypeptide copolymer for intracellular drug delivery. Polymer,2011,52(16):3580-3586
[242] Y. Luk, M. Kato, M. Mrksich, Self-Assembled Monolayers of Alkanethiolates PresentingMannitol Groups Are Inert to Protein Adsorption and Cell Attachment. Langmuir,2000,16(24):9604-9608
[243] N. V. Efremova, S. R. Sheth, D. E. Leckband, Protein-Induced Changes in Poly(ethyleneglycol) Brushes: Molecular Weight and Temperature Dependence. Langmuir,2001,17(24):7628-7636
[244] P. S. Xu, G. Bajaj, T. Shugg, et al, Zwitterionic Chitosan Derivatives for pH-SensitiveStealth Coating. Biomacromolecules,2010,11(9):2352-2358
[245] M. E. Napier, J. M. Desimone, Nanoparticle drug delivery platform. Polymer Reviews,2007,47(3):321-327
[246] S. R. Mudshinge, A. B. Deore, S. Patil, et al, Nanoparticles: Emerging carriers for drugdelivery. Saudi Pharm J,2011,19(3):129-141
[247] A. S. Mikhail, C. Allen, Block copolymer micelles for delivery of cancer therapy: Transportat the whole body, tissue and cellular levels. J Control Release,2009,138(3):214-223
[248] M. C. Jones, J. C. Leroux, Polymeric micelles-a new generation of colloidal drug carriers.European Journal of Pharmaceutics and Biopharmaceutics,1999,48(2):101-111
[249] Y. Q. Shen, E. L. Jin, B. Zhang, et al, Prodrugs Forming High Drug LoadingMultifunctional Nanocapsules for Intracellular Cancer Drug Delivery. J Am Chem Soc,2010,132(12):4259-4265
[250] L. Bildstein, C. Dubernet, P. Couvreur, Prodrug-based intracellular delivery of anticanceragents. Adv Drug Deliver Rev,2011,63(1-2):3-23
[251] G. L. Li, J. Y. Liu, Y. Pang, et al, Polymeric Micelles with Water-Insoluble Drug asHydrophobic Moiety for Drug Delivery. Biomacromolecules,2011,12(6):2016-2026
[252] J. A. MacKay, M. N. Chen, J. R. McDaniel, et al, Self-assembling chimericpolypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.Nature Materials,2009,8(12):993-999
[253] H. S. Yoo, T. G. Park, Folate-receptor-targeted delivery of doxorubicin nano-aggregatesstabilized by doxorubicin-PEG-folate conjugate. J Control Release,2004,100(2):247-256
[254] G. Y. Lee, K. Park, S. Y. Kim, et al, MMPs-specific PEGylated peptide-DOX conjugatemicelles that can contain free doxorubicin. European Journal of Pharmaceutics andBiopharmaceutics,2007,67:646-654
[255] A. S. Mikhail, C. Allen, Poly(ethylene glycol)-b-poly(epsilon-caprolactone) MicellesContaining Chemically Conjugated and Physically Entrapped Docetaxel: Synthesis,Characterization, and the Influence of the Drug on Micelle Morphology. Biomacromolecules,2010,11(5):1273-1280
[256] S. Fukushima, M. Machida, T. Akutsu, et al, Roles of adriamycin and adriamycin dimer inantitumor activity of the polymeric micelle carrier system. Colloid Surface B,1999,16(1-4):227-236
[257] T. Nakanishi, S. Fukushima, K. Okamoto, et al, Development of the polymer micelle carriersystem for doxorubicin. J Control Release,2001,74(1-3):295-302
[258] L. Zhou, R. Cheng, H. Tao, et al, Endosomal pH-Activatable Poly(ethyleneoxide)-graft-Doxorubicin Prodrugs: Synthesis, Drug Release, and Biodistribution inTumor-Bearing Mice. Biomacromolecules,2011,12(5)
[259] M. Hruby, C. Konak, K. Ulbrich, Polymeric micellar pH-sensitive drug delivery system fordoxorubicin. J Control Release,2005,103(1):137-148
[260] T. B. Ren, Y. Feng, H. Q. Dong, et al, Sheddable Nanoparticles for Biomedical Application.Progress in Chemistry,2011,23(1):213-220
[261] H. Cheng, J. L. Zhu, X. Zeng, et al, Targeted Gene Delivery Mediated byFolate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity. BioconjugateChem,2009,20(3):481-487
[262] A. S. Hoffman, Hydrogels for biomedical applications. Ann Ny Acad Sci,2001,944:62-73
[2] M. L. Rogers, R. A. Rush, Non-viral gene therapy for neurological diseases, with an emphasison targeted gene delivery. J Control Release,2012,157(2):183-189
[3] M. J. Tiera, Q. Shi, F. M. Winnik, et al, Polycation-Based Gene Therapy: Current Knowledgeand New Perspectives. Curr Gene Ther,2011,11(4):288-306
[4] N. J. Boylan, A. J. Kim, J. S. Suk, et al, Enhancement of airway gene transfer by DNAnanoparticles using a pH-responsive block copolymer of polyethylene glycol and poly-L-lysine.Biomaterials,2012,33(7):2361-2371
[5] J. Du, Y. Sun, Q. S. Shi, et al, Biodegradable Nanoparticles of mPEG-PLGA-PLL TriblockCopolymers as Novel Non-Viral Vectors for Improving siRNA Delivery and Gene Silencing. Int JMol Sci,2012,13(1):516-533
[6] K. Itaka, K. Yamauchi, A. Harada, et al, Polyion complex micelles from plasmid DNA andpoly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system:physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials,2003,24(24):4495-4506
[7] Y. C. Huang, Y. S. Yang, T. Y. Lai, et al, Lysine-block-tyrosine block copolypeptides:Self-assembly, cross-linking, and conjugation of targeted ligand for drug encapsulation. Polymer,2012,53(4):913-922
[8] D. W. Pack, D. Putnam, R. Langer, Design of imidazole-containing endosomolyticbiopolymers for gene delivery. Biotechnol Bioeng,2000,67(2):217-223
[9] C. Pichon, C. Goncalves, P. Midoux, Histidine-rich peptides and polymers for nucleic acidsdelivery. Adv Drug Deliver Rev,2001,53(1):75-94
[10] I. K. Park, K. Singha, R. B. Arote, et al, pH-Responsive Polymers as Gene Carriers.Macromol Rapid Comm,2010,31(13):1122-1133
[11] S. B. Wang, F. H. Xu, H. S. He, et al, Novel alginate-poly(L-histidine) microcapsules as drugcarriers: In vitro protein release and short term stability. Macromol Biosci,2005,5(5):408-414
[12] E. S. Lee, K. T. Oh, D. Kim, et al, Tumor pH-responsive flower-like micelles of poly(L-lacticacid)-b-poly (ethylene glycol)-b-poly(L-histidine). J Control Release,2007,123(1):19-26
[13] J. Rodriguez-Hernandez, S. Lecommandoux, Reversible inside-out micellization ofpH-responsive and water-soluble vesicles based on polypeptide diblock copolymers. J Am ChemSoc,2005,127(7):2026-2027
[14] T. Thambi, H. Y. Yoon, K. Kim, et al, Bioreducible Block Copolymers Based onPoly(Ethylene Glycol) and Poly(gamma-Benzyl L-Glutamate) for Intracellular Delivery ofCamptothecin. Bioconjugate Chem,2011,22(10):1924-1931
[15] C. Sanson, C. Schatz, J. F. Le Meins, et al, A simple method to achieve high doxorubicinloading in biodegradable polymersomes. J Control Release,2010,147(3):428-435
[16] Y. Wang, Y. N. Wang, G. L. Wu, et al, pH-Responsive Self-Assembly and conformationaltransition of partially propyl-esterified poly(alpha,beta-L-aspartic acid) as amphiphilicbiodegradable polyanion. Colloid Surface B,2009,68(1):13-19
[17] G. L. Zhang, J. B. Ma, Y. H. Li, et al, Synthesis and characterization ofpoly(L-alanine)-block-poly(ethylene glycol) monomethyl ether as amphiphilic biodegradableco-polymers. J Biomat Sci-Polym E,2003,14(12):1389-1400
[18] S. F. Yu, X. Gu, G. L. Wu, et al, Preparation and pH-Sensitive Drug Delivery Study ofmPEG-poly(Imidazole Propyl-Asparagine)-poly(L-Alanine). Acta Chim Sinica,2012,70(2):177-182
[19] H. R. Kricheldorf, Polypeptides and100years of chemistry of alpha-amino acidN-carboxyanhydrides. Angew Chem Int Edit,2006,45(35):5752-5784
[20] Schwmborn M, Degradation of polyaspartamides in vivo. Polym Degrad Stab,1998,59:39-50
[21]杨直, alpha,beta-聚[(N-羟丙基/氨乙基)-DL-天冬酰胺-CO-L-赖氨酸]:作为潜在的非病毒性基因载体的研究.浙江大学硕士毕业论文,2003
[22] H. Shinoda, Y. Asou, A. Suetsugu, et al, Synthesis and characterization of amphiphilicbiodegradable copolymer, poly(aspartic acid-co-lactic acid). Macromol Biosci,2003,3(1):34-43
[23] R. R. Ye, Z. Y. Wang, Q. F. Wang, et al, Synthesis of Biodegradable Material Poly(lacticacid-co-aspartic acid) via Direct Melt Polycondensation and Its Characterization. J Appl PolymSci,2011,121(6):3662-3668
[24] N. Nishiyama, K. Kataoka, Current state, achievements, and future prospects of polymericmicelles as nanocarriers for drug and gene delivery. Pharmacol Therapeut,2006,112(3):630-648
[25] M. Kumagai, Y. Imai, T. Nakamura, et al, Iron hydroxide nanoparticles coated withpoly(ethylene glycol)-poly(aspartic acid) block copolymer as novel magnetic resonance contrastagents for in vivo cancer imaging. Colloid Surface B,2007,56(1-2):174-181
[26] Y. Bae, K. Kataoka, Intelligent polymeric micelles from functional poly(ethyleneglycol)-poly(amino acid) block copolymers. Adv Drug Deliver Rev,2009,61(10):768-784
[27] K. Itaka, T. Ishii, Y. Hasegawa, et al, Biodegradable polyamino acid-based polycations assafe and effective gene carrier minimizing cumulative toxicity. Biomaterials,2010,31(13):3707-3714
[28] T. C. Lai, Y. Bae, T. Yoshida, et al, pH-Sensitive Multi-PEGylated Block Copolymer as aBioresponsive pDNA Delivery Vector. Pharm Res-Dordr,2010,27(11):2260-2273
[29] M. Oba, K. Miyata, K. Osada, et al, Polyplex micelles prepared from omega-cholesterylPEG-polycation block copolymers for systemic gene delivery. Biomaterials,2011,32(2):652-663
[30] G. Antoni, P. Neri, F. Benvenuti, et al, Synthesis of α, β-poly［(2-hydroxyethyl)-DL-aspartamide], a new plasma. J Med Chem,1973,16:893-904
[31]王勇;王亦农;伍国琳等,聚(α,β-L-天冬氨酸丁酯)的合成及水解降解行为研究.离子交换与吸附,2011,27:10-17
[32] M. Fresta, G. Cavallaro, G. Giammona, et al, Preparation and characterization ofpolyethyl-2-cyanoacrylate nanocapsules containing antiepileptic drugs. Biomaterials,1996,17(8):751-758
[33] G. Giammona, V. Tomarchio, G. Pitarresi, et al, Acryloylated alpha,beta-poly(N,hydroxyethyl)-DL-aspartamide and alpha,beta-polyasparthydrazide. Synthesis,characterization and radiation formation of polymeric networks. Colloid&Polymer Science,1997,275(1)
[34] T. Coviello, Y. Yuguchi, K. Kajiwara, et al, Conformational analysis ofalpha,beta-poly(N-hydroxyethyl)-dl-aspartamide (PHEA) and alpha,beta-polyasparthydrazide(PAHy) polymers in aqueous solution. Polymer,1998,39(17):4159-4164
[35] G. Giammona, G. Cavallaro, G. Fontana, et al, Coupling of the antiviral agent zidovudine topolyaspartamide and in vitro drug release studies. J Control Release,1998,54(3):321-331
[36] G. Giammona, G. Pitarresi, G. Cavallaro, et al, New biodegradable hydrogels based on aphotocrosslinkable modified polyaspartamide: synthesis and characterization. Biochimica EtBiophysica Acta-General Subjects,1999,1428(1):29-38
[37] R. Mendichi, G. Giammona, G. Cavallaro, et al, Molecular characterization ofalpha,beta-poly(asparthylhydrazide) a new synthetic polymer for biomedical applications.Polymer,1999,40(25):7109-7116
[38] G. Giammona, G. Cavallaro, G. Pitarresi, et al, Cationic copolymers ofalpha,beta-poly-(N-2-hydroxyethyl)-DL-aspartamide (PHEA) andalpha,beta-polyasparthylhydrazide (PAHy): synthesis and characterization. Polymer International,2000,49(1):93-98
[39] P. Caliceti, S. M. Quarta, F. M. Veronese, et al, Synthesis and biopharmaceuticalcharacterisation of new poly(hydroxyethylaspartamide) copolymers as drug carriers. BiochimicaEt Biophysica Acta-General Subjects,2001,1528(2-3):177-186
[40] R. Muzzalupo, F. Iemma, N. Picci, et al, Novel water-swellable beads based on anacryloylated polyaspartamide. Colloid and Polymer Science,2001,279(7):688-695
[41] E. Pedone, G. Cavallaro, S. C. W. Richardson, et al,alpha,beta-poly(asparthylhydrazide)-glycidyltrimethylammonium chloride copolymers(PAHy-GTA): novel polymers with potential for DNA delivery. J Control Release,2001,77(1-2):139-153
[42] G. Cavallaro, M. Licciardi, G. Giammona, et al, Poly(hydroxyethyl aspartamide) derivativesas colloidal drug carrier systems. J Control Release,2003,89(2):285-295
[43] R. Mendichi, A. G. Schieroni, G. Cavallaro, et al, Molecular characterization ofalpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide derivatives as potential self-assemblingcopolymers forming polymeric micelles. Polymer,2003,44(17):4871-4879
[44] G. Cavallaro, M. Licciardi, P. Caliceti, et al, Synthesis, physico-chemical and biologicalcharacterization of a paclitaxel macromolecular prodrug. European Journal of Pharmaceutics andBiopharmaceutics,2004,58(1):151-159
[45] G. Cavallaro, L. Maniscalco, P. Caliceti, et al, Glycosilated macromolecular conjugates ofantiviral drugs with a polyaspartamide. Journal of Drug Targeting,2004,12(9-10):593-605
[46] G. Cavallaro, L. Maniscalco, G. Giammona, et al, Chemical conjugation of dexamethasone toa polyaspartamide and in vitro evaluation studies. Journal of Drug Delivery Science andTechnology,2004,14(5):373-381
[47] G. Cavallaro, L. Maniscalco, M. Licciardi, et al, Tamoxifen-loaded polymeric micelles:Preparation, physico-chemical characterization and in vitro evaluation studies. Macromol Biosci,2004,4(11):1028-1038
[48] E. F. Craparo, G. Cavallaro, M. L. Bondi, et al, Preparation of polymeric nanoparticles byphoto-crosslinking of an acryloylated polyaspartamide in w/o microemulsion. MacromolecularChemistry and Physics,2004,205(14):1955-1964
[49] G. Pitarresi, P. Pierro, G. Tripodo, et al, Drug delivery from mucoadhesive disks based on aphoto-cross-linkable polyaspartamide derivative. Journal of Drug Delivery Science andTechnology,2005,15(5):377-382
[50] E. F. Craparo, G. Cavallaro, M. L. Bondi, et al, PEGylated nanoparticles based on apolyaspartamide. Preparation, physico-chemical characterization, and intracellular uptake.Biomacromolecules,2006,7(11):3083-3092
[51] G. Giammona, G. Cavallaro, L. Maniscalco, et al, Synthesis and characterisation of novelchemical conjugates based on alpha,beta-polyaspartylhydrazide and beta-cyclodextrins. EuropeanPolymer Journal,2006,42(10):2715-2729
[52] G. Giammona, M. Licciardi, M. Campisi, et al, Synthesis and characterization ofpolyaminoacidic polycations for gene delivery. Biomaterials,2006,27(9)
[53] M. L. T. Liveri, G. Cavallaro, G. Giammona, et al, Amphiphilic derivatives of apolyaspartamide: their aggregation and solubilization ability. Colloids and Surfaces A(Physicochemical and Engineering Aspects),2006,289(1-3)
[54] G. Cavallaro, M. Licciardi, S. Scire, et al, New pegylated polyaspartamide-based polyplexesas gene delivery vectors. Nanomedicine,2010,5(2):243-258
[55] Y. Fernandez, E. Mottini, L. Pasotti, et al, Multicomponent polymeric micelles based onpolyaspartamide as tunable fluorescent pH-window biosensors. Biosensors&Bioelectronics,2010,26(1):29-35
[56] M. Licciardi, G. Cavallaro, M. D. Stefano, et al, New self-assembling polyaspartylhydrazidecopolymer micelles for anticancer drug delivery. International Journal of Pharmaceutics,2010,396(1-2):219-228
[57] M. Licciardi, D. Paolino, C. Celia, et al, Folate-targeted supramolecular vesicular aggregatesbased on polyaspartyl-hydrazide copolymers for the selective delivery of antitumoral drugs.Biomaterials,2010,31(28):7340-7354
[58] M. Licciardi, G. Cavallaro, M. D. Stefano, et al, Polyaspartamide-graft-PolymethacrylateNanoparticles for Doxorubicin Delivery. Macromol Biosci,2011,11(3):445-454
[59] M. C. Ognibene, F. Rocco, E. F. Craparo, et al, Biocompatible Micelles Based on SqualenePortions Linked to PEGylated Polyaspartamide as Potential Colloidal Drug Carriers. CurrentNanoscience,2011,7(5):747-756
[60] M. G. Sarpietro, G. Pitarresi, S. Ottimo, et al, Interaction between Drug LoadedPolyaspartamide-Polylactide-Polysorbate Based Micelles and Cell Membrane Models: ACalorimetric Study. Molecular Pharmaceutics,2011,8(3):642-650
[61] S. R. Yang, S. B. Kim, C. O. Joe, et al, Self-aggregates of oligoarginine-conjugatedpoly(amino acid) derivatives as a carrier for intracellular drug delivery. Biotechnol Lett,2005,27(14):977-982
[62] H. M. Yang, H. J. Lee, K. S. Jang, et al, Poly(amino acid)-coated iron oxide nanoparticles asultra-small magnetic resonance probes. J Mater Chem,2009,19(26):4566-4574
[63] B. Jung, C. Y. Baek, J. Y. Yang, et al, Anticancer therapeutic self-aggregates of sphingolipidmetabolite-grafted poly(amino acid)-derivative and their enhanced intracellular delivery. J IndEng Chem,2010,16(6):1011-1018
[64] H. W. Park, H. S. Jin, S. Y. Yang, et al, Tunable phase transition behaviors of pH-sensitivepolyaspartamides having various cationic pendant groups. Colloid and Polymer Science,2009,287(8):919-926
[65] K. Seo, J. D. Kim, D. Kim, pH-dependent self-assembling behavior of imidazole-containingpolyaspartamide derivatives. J Biomed Mater Res A,2009,90A(2):478-486
[66] K. Seo, D. Kim, pH-dependent hemolysis of biocompatible imidazole-graftedpolyaspartamide derivatives. Acta Biomater,2010,6(6):2157-2164
[67] S. Kim, J. H. Kim, D. Kim, pH sensitive swelling and releasing behavior of nano-gels basedon polyaspartamide graft copolymers. J Colloid Interf Sci,2011,356(1):100-106
[68] W. Lin, D. Kim, pH-Sensitive Micelles with Cross-Linked Cores Formed fromPolyaspartamide Derivatives for Drug Delivery. Langmuir,2011,27(19):12090-12097
[69] H. M. Yang, C. W. Park, M. A. Woo, et al, HER2/neu Antibody Conjugated Poly(aminoacid)-Coated Iron Oxide Nanoparticles for Breast Cancer MR Imaging. Biomacromolecules,2010,11(11):2866-2872
[70] H. M. Yang, B. C. Oh, J. H. Kim, et al, Multifunctional poly(aspartic acid) nanoparticlescontaining iron oxide nanocrystals and doxorubicin for simultaneous cancer diagnosis and therapy.Colloid Surface A,2011,391(1-3):208-215
[71] S. R. Yang, H. J. Lee, J. D. Kim, Histidine-conjugated poly(amino acid) derivatives for thenovel endosomolytic delivery carrier of doxorubicin. J Control Release,2006,114(1):60-68
[72] R. Duncan, The dawning era of polymer therapeutics. Nat Rev Drug Discov,2003,2(5):347-360
[73] F. Greco, M. J. Vicent, Combination therapy: Opportunities and challenges for polymer-drugconjugates as anticancer nanomedicines. Adv Drug Deliver Rev,2009,61(13):1203-1213
[74] Y. Bae, S. Fukushima, A. Harada, et al, Design of environment-sensitive supramolecularassemblies for intracellular drug delivery: Polymeric micelles that are responsive to intracellularpH change. Angew Chem Int Edit,2003,42(38):4640-4643
[75] Y. Bae, W. D. Jang, N. Nishiyama, et al, Multifunctional polymeric micelles withfolate-mediated cancer cell targeting and pH-triggered drug releasing properties for activeintracellular drug delivery. Molecular Biosystems,2005,1(3):242-250
[76] Y. Bae, N. Nishiyama, S. Fukushima, et al, Preparation and biological characterization ofpolymeric micelle drug carriers with intracellular pH-triggered drug release property: Tumorpermeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy.Bioconjugate Chem,2005,16(1):122-130
[77] P. Bawa, V. Pillay, Y. E. Choonara, et al, Stimuli-responsive polymers and their applicationsin drug delivery. Biomedical Materials,2009,4(2)
[78] Y. Chan, T. Wong, F. Byrne, et al, Acid-labile core cross-linked micelles for pH-triggeredrelease of antitumor drugs. Biomacromolecules,2008,9(7):1826-1836
[79] F. Corbellini, R. M. A. Knegtel, P. D. J. Grootenhuis, et al, Water-soluble molecular capsules:Self-assembly and binding properties. Chemistry-a European Journal,2005,11(1):298-307
[80] S. R. Croy, G. S. Kwon, Polymeric micelles for drug delivery. Current Pharmaceutical Design,2006,12(36):4669-4684
[81] M. Das, S. Mardyani, W. C. W. Chan, et al, Biofunctionalized pH-responsive microgels forcancer cell targeting: Rational design. Advanced Materials,2006,18(1):80-83
[82] E. R. Gillies, J. M. J. Frechet, pH-responsive copolymer assemblies for controlled release ofdoxorubicin. Bioconjugate Chem,2005,16(2):361-368
[83] J. X. Gu, W. P. Cheng, J. G. Liu, et al, pH-triggered reversible "stealth" polycationic micelles.Biomacromolecules,2008,9(1):255-262
[84] R. Haag, Supramolecular drug-delivery systems based on polymeric core-shell architectures.Angew Chem Int Edit,2004,43(3):278-282
[85] R. Haag, F. Kratz, Polymer therapeutics: Concepts and applications. Angew Chem Int Edit,2006,45(8):1198-1215
[86] J. M. Hu, S. Y. Liu, Responsive Polymers for Detection and Sensing Applications: CurrentStatus and Future Developments. Macromolecules,2010,43(20):8315-8330
[87] E. S. Lee, Z. G. Gao, Y. H. Bae, Recent progress in tumor pH targeting nanotechnology. JControl Release,2008,132(3):164-170
[88] A. Mahmud, X. B. Xiong, H. M. Aliabadi, et al, Polymeric micelles for drug targeting.Journal of Drug Targeting,2007,15(9):553-584
[89] J. K. Oh, R. Drumright, D. J. Siegwart, et al, The development of microgels/nanogels fordrug delivery applications. Progress in Polymer Science,2008,33(4):448-477
[90] K. T. Oh, H. Q. Yin, E. S. Lee, et al, Polymeric nanovehicles for anticancer drugs withtriggering release mechanisms. J Mater Chem,2007,17(38):3987-4001
[91] M. Oishi, H. Hayashi, I. D. Michihiro, et al, Endosomal release and intracellular delivery ofanticancer drugs using pH-sensitive PEGylated nanogels. J Mater Chem,2007,17(35):3720-3725
[92] N. Rapoport, Physical stimuli-responsive polymeric micelles for anti-cancer drug delivery.Progress in Polymer Science,2007,32(8-9):962-990
[93] C. J. F. Rijcken, O. Soga, W. E. Hennink, et al, Triggered destabilisation of polymericmicelles and vesicles by changing polymers polarity: An attractive tool for drug delivery. JControl Release,2007,120(3):131-148
[94] R. Tong, J. J. Cheng, Anticancer polymeric nanomedicines. Polymer Reviews,2007,47(3):345-381
[95] C. H. Wang, G. H. Hsiue, Polymeric micelles with a pH-responsive structure as intracellulardrug carriers. J Control Release,2005,108(1):140-149
[96] N. Wiradharma, Y. Zhang, S. Venkataraman, et al, Self-assembled polymer nanostructures fordelivery of anticancer therapeutics. Nano Today,2009,4(4):302-317
[97] Q. Yang, S. H. Wang, P. W. Fan, et al, pH-responsive carrier system based on carboxylic acidmodified mesoporous silica and polyelectrolyte for drug delivery. Chemistry of Materials,2005,17(24):5999-6003
[98] Z. Amoozgar, Y. Yeo, Recent advances in stealth coating of nanoparticle drug deliverysystems. Wiley Interdisciplinary Reviews-Nanomedicine and Nanobiotechnology,2012,4(2):219-233
[99] T. Kaasgaard, T. L. Andresen, Liposomal cancer therapy: exploiting tumor characteristics.Expert Opin Drug Del,2010,7(2):225-243
[100] C. Li, S. Wallace, Polymer-drug conjugates: Recent development in clinical oncology. AdvDrug Deliver Rev,2008,60(8):886-898
[101] W. B. Liechty, N. A. Peppas, Expert opinion: Responsive polymer nanoparticles in cancertherapy. European Journal of Pharmaceutics and Biopharmaceutics,2012,80(2):241-246
[102] W. W. Gao, J. M. Chan, O. C. Farokhzad, pH-Responsive Nanoparticles for Drug Delivery.Molecular Pharmaceutics,2010,7(6):1913-1920
[103] S. Asayama, H. Kato, H. Kawakami, et al, Carboxymethyl poly(L-histidine) as a newpH-sensitive polypeptide at endosomal/lysosomal pH. Polymers for Advanced Technologies,2007,18(4):329-333
[104] G. Mohajer, E. S. Lee, Y. H. Bae, Enhanced intercellular retention activity of novelpH-sensitive polymeric micelles in wild and multidrug resistant MCF-7cells. Pharm Res-Dordr,2007,24(9):1618-1627
[105] A. Taluja, Y. H. Bae, Role of a novel excipient poly(ethylene Glycol)-b-poly(L-histidine) inretention of physical stability of insulin in aqueous solutions. Pharm Res-Dordr,2007,24(8):1517-1526
[106] M. Casolaro, Y. Ito, T. Ishii, et al, Stimuli-responsive poly(ampholyte)s containingL-histidine residues: synthesis and protonation thermodynamics of methacrylic polymers in thefree and in the cross-linked gel forms. Express Polymer Letters,2008,2(3):165-183
[107] D. Kim, E. S. Lee, K. Park, et al, Doxorubicin Loaded pH-sensitive Micelle: AntitumoralEfficacy against Ovarian A2780/DOX(R) Tumor. Pharm Res-Dordr,2008,25(9):2074-2082
[108] E. S. Lee, Z. G. Gao, D. Kim, et al, Super pH-sensitive multifunctional polymeric micellefor tumor pH(e) specific TAT exposure and multidrug resistance. J Control Release,2008,129(3):228-236
[109] K. T. Oh, E. S. Lee, Cancer-associated pH-responsive tetracopolymeric micelles composedof poly(ethylene glycol)-b-poly(L-histidine)-b-poly(L-lactic acid)-b-poly(ethylene glycol).Polymers for Advanced Technologies,2008,19(12):1907-1913
[110] K. T. Oh, E. S. Lee, D. Kim, et al, L-Histidine-based pH-sensitive anticancer drug carriermicelle: Reconstitution and brief evaluation of its systemic toxicity. International Journal ofPharmaceutics,2008,358(1-2):177-183
[111] H. Q. Yin, E. S. Lee, D. Kim, et al, Physicochemical characteristics of pH-sensitivepoly(L-Histidine)-b-poly (ethylene glycol)/poly(L-Lactide)-b-poly(ethylene glycol) mixedmicelles. J Control Release,2008,126(2):130-138
[112] K. T. Oh, D. Kim, H. H. You, et al, pH-sensitive properties of surface charge-switchedmultifunctional polymeric micelle. International Journal of Pharmaceutics,2009,376(1-2):134-140
[113] H. Q. Yin, Y. H. Bae, Physicochemical aspects of doxorubicin-loaded pH-sensitivepolymeric micelle formulations from a mixture ofpoly(L-histidine)-b-poly(L-lactide)-b-poly(ethylene glycol). European Journal of Pharmaceuticsand Biopharmaceutics,2009,71(2):223-230
[114] P. Dutta, J. Dey, Drug solubilization by amino acid based polymeric nanoparticles:Characterization and biocompatibility studies. International Journal of Pharmaceutics,2011,421(2):353-363
[115] Z. G. Gao, L. Tian, J. Hu, et al, Prevention of metastasis in a4T1murine breast cancermodel by doxorubicin carried by folate conjugated pH sensitive polymeric micelles. J ControlRelease,2011,152(1):84-89
[116] R. Liu, D. Li, B. He, et al, Anti-tumor drug delivery of pH-sensitive poly(ethyleneglycol)-poly(L-histidine-)-poly(L-lactide) nanoparticles. J Control Release,2011,152(1):49-56
[117] F. X. Zhan, W. Chen, Z. J. Wang, et al, Acid-Activatable Prodrug Nanogels for EfficientIntracellular Doxorubicin Release. Biomacromolecules,2011,12(10):3612-3620
[118] T. Etrych, M. Jelinkova, B. Rihova, et al, New HPMA copolymers containing doxorubicinbound via pH-sensitive linkage: synthesis and preliminary in vitro and in vivo biologicalproperties. J Control Release,2001,73(1):89-102
[119] C. X. Ding, J. X. Gu, X. Z. Qu, et al, Preparation of Multifunctional Drug Carrier forTumor-Specific Uptake and Enhanced Intracellular Delivery through the Conjugation of WeakAcid Labile Linker. Bioconjugate Chem,2009,20(6):1163-1170
[120] E. R. Gillies and J. M. J. Fréchet, pH-Responsive Copolymer Assemblies for ControlledRelease of Doxorubicin. Bioconjugate Chem,2005,16(2):361-368
[121] R. P. Tang, W. H. Ji, D. Panus, et al, Block copolymer micelles with acid-labile ortho esterside-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells. JControl Release,2011,151(1):18-27
[122] H. Cabral, K. Kataoka, Multifunctional nanoassemblies of block copolymers for futurecancer therapy. Science and Technology of Advanced Materials,2010,11(1)
[123] Rong Tong, David A. Christian, Li Tang, et al, Nanopolymeric Therapeutics. Mrs Bulletin,2009,34(6):422-431
[124] M. Zhang, K. Kataoka, Nano-structured composites based on calcium phosphate for cellulardelivery of therapeutic and diagnostic agents. Nano Today,2009,4(6):508-517
[125] K. Osada, R. J. Christie, K. Kataoka, Polymeric micelles from poly(ethyleneglycol)-poly(amino acid) block copolymer for drug and gene delivery. Journal of the RoyalSociety Interface,2009,6:S325-S339
[126] R. Scherer, J. Kreuter, Influence of enzymes on the stability of poly butylcyanoacrylatenanoparticles. Int J Pharm,1994,101:165-176
[127]王成运;公彦宝;刘顺英等, α,β-聚[N-(丁二酸基)-L-天冬酰胺]的合成及其顺铂大分子药物的细胞毒性.高等化学学报,2008,29:1665-1670
[128] S. J. Lee, K. H. Min, H. J. Lee, et al, Ketal Cross-Linked Poly(ethylene glycol)-Poly(aminoacid)s Copolymer Micelles for Efficient Intracellular Delivery of Doxorubicin.Biomacromolecules,2011,12(4):1224-1233
[129] C. L. Wu, H. He, H. J. Gao, et al, Synthesis of Fe(3)O(4)@SiO(2)@polymer nanoparticlesfor controlled drug release. Sci China Chem,2010,53(3):514-518
[130] Y. K. Xue, X. X. Tang, J. Huang, et al, Anti-tumor efficacy of polymer-platinum(II)complex micelles fabricated from folate conjugated PEG-graft-alpha,beta-poly [(N-aminoacidyl)-aspartamide] and cis-dichlorodiammine platinum(II) in tumor-bearing mice. ColloidSurface B,2011,85(2):280-288
[131] M. Yokoyama, S. Fukushima, R. Uehara, et al, Characterization of physical entrapment andchemical conjugation of adriamycin in polymeric micelles and their design for in vivo delivery toa solid tumor. J Control Release,1998,50(1-3):79-92
[132] J. Cabral, S. C. Moratti, Hydrogels for biomedical applications. Future Med Chem,2011,3(15):1877-1888
[133] J. Jagur-Grodzinski, Polymeric gels and hydrogels for biomedical and pharmaceuticalapplications. Polymers for Advanced Technologies,2010,21(1):27-47
[134] I. Tomatsu, K. Peng, A. Kros, Photoresponsive hydrogels for biomedical applications. AdvDrug Deliver Rev,2011,63(14-15):1257-1266
[135] F. Chiellini, R. Bizzarri, C. K. Ober, et al, Patterning of polymeric hydrogels for biomedicalapplications. Macromol Rapid Comm,2001,22(15):1284-1287
[136] L. H. Zhou, G. Y. Huang, S. Q. Wang, et al, Advances in cell-based biosensors usingthree-dimensional cell-encapsulating hydrogels. Biotechnol J,2011,6(12):1466-1476
[137] A. Wadee, V. Pillay, Y. E. Choonara, et al, Recent advances in the design of drug-loadedpolymeric implants for the treatment of solid tumors. Expert Opin Drug Del,2011,8(10):1323-1340
[138] P. BARTL O. WICHTERLE, M. ROSENBERG, Water-Soluble Methacrylates asEmbedding Media for Preparation of Ultra-Thin Sections. Nature,1960,186:494-495
[139] D. LiM O. WICHTERLE, Hydrophilic Gels for Biological Use. Nature,1960,185:117-118
[140] W. A. Laftah, S. Hashim, A. N. Ibrahim, Polymer Hydrogels: A Review. Polym-PlastTechnol,2011,50(14):1475-1486
[141] S. N. Pawar, K. J. Edgar, Alginate derivatization: A review of chemistry, properties andapplications. Biomaterials,2012,33(11):3279-3305
[142] X. Xu, A. K. Jha, D. A. Harrington, et al, Hyaluronic acid-based hydrogels: from a naturalpolysaccharide to complex networks. Soft Matter,2012,8(12):3280-3294
[143] H. T. Ta, C. R. Dass, D. E. Dunstan, Injectable chitosan hydrogels for localised cancertherapy. J Control Release,2008,126(3):205-216
[144] C. W. Zhao, X. L. Zhuang, P. He, et al, Synthesis of biodegradable thermo-andpH-responsive hydrogels for controlled drug release. Polymer,2009,50(18):4308-4316
[145] H. B. Zhang, C. Zhao, H. Cao, et al, Hyperbranched poly(amine-ester) based hydrogels forcontrolled multi-drug release in combination chemotherapy. Biomaterials,2010,31(20):5445-5454
[146] D. A. Ossipov, S. Piskounova, J. Hilborn, Poly(vinyl alcohol) cross-linkers for in vivoinjectable hydrogels. Macromolecules,2008,41(11):3971-3982
[147] J. H. Ahn, Y. S. Jeon, D. J. Chung, et al, Preparation and Swelling Behavior ofStimuli-responsive PHEMA Hybrid Gels. Polym-Korea,2011,35(1):94-98
[148] D. D. Diaz, D. Kuhbeck, R. J. Koopmans, Stimuli-responsive gels as reaction vessels andreusable catalysts. Chem Soc Rev,2011,40(1):427-448
[149] T. Z. Grove, C. O. Osuji, J. D. Forster, et al, Stimuli-Responsive Smart Gels Realized viaModular Protein Design. J Am Chem Soc,2010,132(40):14024-14026
[150] S. K. Ahn, R. M. Kasi, S. C. Kim, et al, Stimuli-responsive polymer gels. Soft Matter,2008,4(6):1151-1157
[151] M. Toda, F. Tanaka, Mechanically induced helicity in chiral stimuli-responsive gels.Macromolecules,2007,40(13):4703-4709
[152] W. G. Weng, J. B. Beck, A. M. Jamieson, et al, Understanding the mechanism of gelationand stimuli-responsive nature of a class of metallo-supramolecular gels. J Am Chem Soc,2006,128(35):11663-11672
[153] E. Marsano, E. Blanchi, S. Vicini, et al, Stimuli responsive gels based on interpenetratingnetwork of chitosan and poly(vinylpyrrolidone). Polymer,2005,46(5):1595-1600
[154] H. J. Kim, J. H. Lee, M. Lee, Stimuli-responsive gels from reversible coordination polymers.Angew Chem Int Edit,2005,44(36):5810-5814
[155] M. Burt, B. C. Dave, Use of stimuli-responsive organosilica sol-gels in detection andsensing.2004. Abstr Pap Am Chem S,2004,227:U492-U492
[156] B. C. Dave, M. S. Rao, Use of stimuli-responsive organosilica sol-gels in separation/releaseof molecules. Abstr Pap Am Chem S,2004,227:U891-U891
[157] E. Marsano, E. Bianchi, A. Viscardi, Stimuli responsive gels based on interpenetratingnetwork of hydroxy propylcellulose and poly (N-isopropylacrylamide). Polymer,2004,45(1):157-163
[158] Y. H. Ma, Y. Q. Tang, N. C. Billingham, et al, Synthesis of biocompatible,stimuli-responsive, physical gels based on ABA triblock copolymers. Biomacromolecules,2003,4(4):864-868
[159] H. Goto, H. Q. Zhang, E. Yashima, Chiral stimuli-responsive gels: Helicity induction inpoly(phenylacetylene) gels bearing a carboxyl group with chiral amines. J Am Chem Soc,2003,125(9):2516-2523
[160] K. Kulbaba, M. J. MacLachlan, C. E. B. Evans, et al, Stimuli-responsive gels based onring-opened polyferrocenes: Synthesis, characterization, and electrochemical studies of swellable,thermally cross-linked polyferrocenylsilanes. Acs Sym Ser,2003,833:175-188
[161] R. Deen, L. H. Gan, Studies of new piperazine based stimuli-responsive gels. Abstr Pap AmChem S,2001,222:U377-U377
[162] L. L. Zhao, L. J. Zhu, F. Y. Liu, et al, pH triggered injectable amphiphilic hydrogelcontaining doxorubicin and paclitaxel. International Journal of Pharmaceutics,2011,410(1-2):83-91
[163] S. H. Nezhadi, P. F. M. Choong, F. Lotfipour, et al, Gelatin-based delivery systems forcancer gene therapy. Journal of Drug Targeting,2009,17(10):731-738
[164] Y. J. Yin, Z. Y. Li, Y. B. Sun, et al, A preliminary study on chitosan/gelatin polyelectrolytecomplex formation.. J Mater Sci,2005,40(17):4649-4652
[165] M. J. Song, D. S. Lee, J. H. Ahn, et al, Dielectric behavior during sol-gel transition ofPEO-PPO-PEO triblock copolymer aqueous solution.. Polym Bull,2000,43(6):497-504
[166] A. Sosnik, D. Cohn, J. S. San Roman, et al, Crosslinkable PEO-PPO-PEO-based reversethermo-responsive gels as potentially injectable materials. J Biomat Sci-Polym E,2003,14(3):227-239
[167] K. P. Schneider, E. Wehrschuetz-Sigl, S. J. Eichhorn, et al, Bioresponsive systems based oncrosslinked polysaccharide hydrogels. Process Biochem,2012,47(2):305-311
[168] G. R. Hendrickson, L. A. Lyon, Bioresponsive hydrogels for sensing applications. SoftMatter,2009,5(1):29-35
[169] R. V. Ulijn, N. Bibi, V. Jayawarna, et al, Bioresponsive hydrogels. Mater Today,2007,10(4):40-48
[170] J. Kim, N. Singh, M. Serpe, et al, Towards the design of bioresponsive hydrogels. Abstr PapAm Chem S,2006,231
[171] D. A. Wang, C. G. Williams, F. Yang, et al, Bioresponsive phosphoester hydrogels for bonetissue engineering. Tissue Eng,2005,11(1-2):201-213
[172] B. R. Nayak, T. L. Lowe, Novel biodegradable-Co-bioresponsive hydrogels for drugdelivery. Abstr Pap Am Chem S,2003,225:U680-U680
[173] A. Matsumoto, K. Yamamoto, R. Yoshida, et al, A totally synthetic glucose responsive geloperating in physiological aqueous conditions. Chem Commun,2010,46(13):2203-2205
[174] R. V. Ulijn, Enzyme-responsive materials: a new class of smart biomaterials. J Mater Chem,2006,16(23):2217-2225
[175] B. Yurke, D. C. Lin, N. A. Langrana, Use of DNA nanodevices in modulating themechanical properties of polyacrylamide gels. Lect Notes Comput Sc,2006,3892:417-426
[176] Y. L. Li, J. Rodrigues, H. Tomas, Injectable and biodegradable hydrogels: gelation,biodegradation and biomedical applications. Chem Soc Rev,2012,41(6):2193-2221
[177] C. T. Huynh, M. K. Nguyen, D. S. Lee, Injectable Block Copolymer Hydrogels:Achievements and Future Challenges for Biomedical Applications. Macromolecules,2011,44(17):6629-6636
[178] D. Macaya, M. Spector, Injectable hydrogel materials for spinal cord regeneration: a review.Biomedical Materials,2012,7(1)
[179] T. Delair, In situ forming polysaccharide-based3D-hydrogels for cell delivery inregenerative medicine. Carbohyd Polym,2012,87(2):1013-1019
[180]曹辉，孙绍华，苏海佳等,聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展.化工进展,2009,28:1991-1994
[181] N. Akinori，T. Hiroaki，A. Masanobu, Superabsorbent polymer and process for producingsame.1995.
[182] V. Torma, T. Gyenes, Z. Szakacs, et al, A novel potentiometric method for the determinationof real crosslinking ratio of poly(aspartic acid) gels. Acta Biomater,2010,6(3):1186-1190
[183] Z. Varga, K. Molnar, V. Torma, et al, Kinetics of volume change of poly(succinimide) gelsduring hydrolysis and swelling. Phys Chem Chem Phys,2010,12(39):12670-12675
[184] T. Gyenes, V. Torma, M. Zrinyi, Swelling properties of aspartic acid-based hydrogels.Colloid Surface A,2008,319(1-3):154-158
[185] T. Gyenes, V. Torma, B. Gyarmati, et al, Synthesis and swelling properties of novelpH-sensitive poly(aspartic acid) gels. Acta Biomater,2008,4(3):733-744
[186] S. W. Yoon, D. J. Chung, J. H. Kim, Preparation and swelling behavior of biodegradablehydrogels based on alpha,beta-poly(N-2-hydroxyethyl-DL-aspartamide). J Appl Polym Sci,2003,90(13):3741-3746
[187] J. H. Kim, J. H. Lee, S. W. Yoon, Preparation and swelling behavior of biodegradablesuperabsorbent gels based on polyaspartic acid. J Ind Eng Chem,2002,8(2):138-142
[188] S. K. Min, S. H. Kim, J. H. Kim, Preparation and swelling behavior of biodegradablepoly(aspartic acid)-based hydrogel. J Ind Eng Chem,2000,6(4):276-279
[189] J. Yang, F. Wang, T. W. Tan, Degradation Behavior of Hydrogel Based on Cross linkedPoly(aspartic acid). J Appl Polym Sci,2010,117(1):178-185
[190] G. Giammona, B. Carlisia, G. Cavallaroa, G., et al, A new water-soluble synthetic polymer,α,β-polyasparthydrazide, as potential plasma expander and drug carrier. J Control Release,1994,29:63-72
[191] G. Pitarresi, F. S. Palumbo, G. Cavallaro, et al, Scaffolds based on hyaluronan crosslinkedwith a polyaminoacid: Novel candidates for tissue engineering application. J Biomed Mater Res A,2008,87A(3):770-779
[192] D. Mandracchia, G. Pitarresi, F. S. Palumbo, et al, PH-Sensitive hydrogel based on a novelphotocross-linkable copolymer. Biomacromolecules,2004,5(5):1973-1982
[193] J. H. Park, J. R. Moon, K. H. Hong, et al, Photo-crosslinked polyaspartamide hybrid gelcontaining thermo-responsive Pluronic triblock copolymer. J Polym Res,2011,18(2):273-278
[194] G. Spadaro， C. Dispenza， G. Giammona, Cytarabine release from α,β-poly(N-hydroxyethyl)-DL-aspartamide matrices cross-linked through γ-radiation. Biomaterials,1996,17:953-958
[195] V. Tomarchio, G. Giammona, G. Pitarresi, et al, Glycidyl methacrylate derivatization ofα,β-poly(N-hydroxyethyl)-dl-aspartamide and α,β-polyasparthydrazide. Polym Bull,1997,38:3315-3323
[196]刘姗,朱健婷,苏海佳, pH敏感型聚天冬氨酸水凝胶制备工艺的优化及其释药性能.材料导报：研究篇,2010,24:100-103
[197] G. Giammona, G. Pitarresi, G. Cavallaro, et al, pH-sensitive hydrogel based on apolyaspartamide derivative. Journal of Drug Delivery Science and Technology,2006,16(1):77-84
[198] G. Giammona, G. Pitarresi, E. F. Craparo, et al, New biodegradable hydrogels based on aphoto-cross-linkable polyaspartamide and poly(ethylene glycol) derivatives. Release studies of ananticancer drug. Colloid and Polymer Science,2001,279(8):771-783
[199] G. Giammona, G. Pitarresi, V. Tomarchio, et al, A hydrogel based on polyaspartamide:Characterization and evaluation of in-vivo biocompatibility and drug release in the rat. Journal ofPharmacy and Pharmacology,1997,49(11):1051-1056
[200]常宪智，于跃芹，田红杰等，聚天冬氨酸交联温敏性水凝胶的药物缓释性能.高分子材料科学与工程，2009，25:79-82
[201] S. Salmaso, R. Schrepfer, G. Cavallaro, et al, Supramolecular association of recombinanthuman growth hormone with hydrophobized polyhydroxyethylaspartamides. European Journal ofPharmaceutics and Biopharmaceutics,2008,68(3):656-666
[202]王健，刘振华，卓仁禧， α，β-聚-DL-天冬酰胺衍生物水凝胶的合成及其溶胀性能研究.高分子学报，1998,5:563-566
[203]吴军，陈强，李利等，可降解聚天冬氨酸水凝胶的制备与应用研究.材料导报，2005,19:126-128
[204] R. Zhang, Z. B. Huang, M. Y. Xue, et al, Detailed characterization of an injectablehyaluronic acid-polyaspartylhydrazide hydrogel for protein delivery. Carbohyd Polym,2011,85(4):717-725
[205] C. Sperling, M. Fischer, M. F. Maitz, et al, Blood coagulation on biomaterials requires thecombination of distinct activation processes. Biomaterials,2009,30(27):4447-4456
[206] P. Aggarwal, J. B. Hall, C. B. McLeland, et al, Nanoparticle interaction with plasmaproteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. AdvDrug Deliver Rev,2009,61(6):428-437
[207] B. Thierry, L. Zimmer, S. McNiven, et al, Electrostatic Self-Assembly of PEG Copolymersonto Porous Silica Nanoparticles. Langmuir,2008,24(15):8143-8150
[208] C. Rodriguez-Emmenegger, A. J ger, E. J ger, et al, Polymeric nanocapsules ultra stable incomplex biological media. Colloids and Surfaces B: Biointerfaces,2011,83(2):376-381
[209] C.B Geer, I.A Rus, S.T Lord, et al, Surface-dependent fibrinopeptide A accessibility tothrombin. Acta Biomater,2007,3(5):663
[210] I. Lynch, A. Salvati, K. A. Dawson, Protein-nanoparticle interactions: What does the cell see.Nat Nano,2009,4(9):546-547
[211] A. E. Nel, L. Madler, D. Velegol, et al, Understanding biophysicochemical interactions atthe nano-bio interface. Nature Materials,2009,8(7):543-557
[212] T. Ren, Y. Feng, H. Dong, et al, Sheddable Nanoparticles for Biomedical Application.Progress in Chemistry,2011,23(1):213-220
[213] B. Romberg, W. E. Hennink, G. Storm, Sheddable coatings for long-circulatingnanoparticles. Pharm Res-Dordr,2008,25(1):55-71
[214] M. Wang, M. Thanou, Targeting nanoparticles to cancer. Pharmacological Research,2010,62(2):90-99
[215] S. Zhang, Y. Shi, C. Huang, et al, Design of spectral reflective properties of the stealthcoating. Acta Physica Sinica,2007,56(9):5508-5512
[216] L. Y. Li, S. F. Chen, J. Zheng, et al, Protein adsorption on oligo(ethylene glycol)-terminatedalkanethiolate self-assembled monolayers: The molecular basis for nonfouling behavior. J PhysChem B,2005,109(7):2934-2941
[217] J. Zheng, L. Y. Li, H. K. Tsao, et al, Strong repulsive forces between protein and oligo(ethylene glycol) self-assembled monolayers: A molecular simulation study. Biophys J,2005,89(1):158-166
[218] D. E. Owens Iii, N. A. Peppas, Opsonization, biodistribution, and pharmacokinetics ofpolymeric nanoparticles. International Journal of Pharmaceutics,2006,307(1):93-102
[219] S. F. Chen, L. Y. Liu, S. Y. Jiang, Strong resistance of oligo(phosphorylcholine)self-assembled monolayers to protein adsorption. Langmuir,2006,22(6):2418-2421
[220] S. F. Chen, J. Zheng, L. Y. Li, et al, Strong resistance of phosphorylcholine self-assembledmonolayers to protein adsorption: Insights into nonfouling properties of zwitterionic materials. JAm Chem Soc,2005,127(41):14473-14478
[221] Y. He, J. Hower, S. F. Chen, et al, Molecular simulation studies of protein interactions withzwitterionic phosphorylcholine self-assembled monolayers in the presence of water. Langmuir,2008,24(18):10358-10364
[222] J. Ladd, Z. Zhang, S. Chen, et al, Zwitterionic polymers exhibiting high resistance tononspecific protein adsorption from human serum and plasma. Biomacromolecules,2008,9(5):1357-1361
[223] G. Cheng, Z. Zhang, S. F. Chen, et al, Inhibition of bacterial adhesion and biofilm formationon zwitterionic surfaces. Biomaterials,2007,28(29):4192-4199
[224] Z. Zhang, G. Cheng, L. R. Carr, et al, The hydrolysis of cationic polycarboxybetaine estersto zwitterionic polycarboxybetaines with controlled properties. Biomaterials,2008,29(36):4719-4725
[225] N. D. Brault, C. L. Gao, H. Xue, et al, Ultra-low fouling and functionalizable zwitterioniccoatings grafted onto SiO(2) via a biomimetic adhesive group for sensing and detection incomplex media. Biosensors&Bioelectronics,2010,25(10):2276-2282
[226] C. L. Gao, G. Z. Li, H. Xue, et al, Functionalizable and ultra-low fouling zwitterionicsurfaces via adhesive mussel mimetic linkages. Biomaterials,2010,31(7):1486-1492
[227] G. Z. Li, G. Cheng, H. Xue, et al, Ultra low fouling zwitterionic polymers with a biomimeticadhesive group. Biomaterials,2008,29(35):4592-4597
[228] W. Yang, L. Zhang, S. L. Wang, et al, Functionalizable and ultra stable nanoparticles coatedwith zwitterionic poly(carboxybetaine) in undiluted blood serum. Biomaterials,2009,30(29):5617-5621
[229] L. Zhang, H. Xue, C. L. Gao, et al, Imaging and cell targeting characteristics of magneticnanoparticles modified by a functionalizable zwitterionic polymer with adhesive3,4-dihydroxyphenyl-L-alanine linkages. Biomaterials,2010,31(25):6582-6588
[230] Z. Q. Cao, Q. M. Yu, H. Xue, et al, Nanoparticles for Drug Delivery Prepared fromAmphiphilic PLGA Zwitterionic Block Copolymers with Sharp Contrast in Polarity between TwoBlocks. Angew Chem Int Edit,2010,49(22):3771-3776
[231] J. Kopecek, P. Kopeckova, HPMA copolymers: Origins, early developments, present, andfuture. Adv Drug Deliver Rev,2010,62(2):122-149
[232] T. Lammers, V. Subr, K. Ulbrich, et al, Simultaneous delivery of doxorubicin andgemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials,2009,30(20):3466-3475
[233] J. M. Metselaar, P. Bruin, L. W. T. de Boer, et al, A novel family of L-amino acid-basedbiodegradable polymer-lipid conjugates for the development of long-circulating liposomes witheffective drug-targeting capacity. Bioconjugate Chem,2003,14(6):1156-1164
[234] B. Romberg, J. M. Metselaar, L. Baranyi, et al, Poly(amino acid)s: Promising enzymaticallydegradable stealth coatings for liposomes. International Journal of Pharmaceutics,2007,331(2):186-189
[235] B. Romberg, C. Oussoren, C. J. Snel, et al, Pharmacokinetics ofpoly(hydroxyethyl-L-asparagine)-coated liposomes is superior over that of PEG-coated liposomesat low lipid dose and upon repeated administration. Bba-Biomembranes,2007,1768(3):737-743
[236] S. F. Chen, Z. Q. Cao, S. Y. Jiang, Ultra-low fouling peptide surfaces derived from naturalamino acids. Biomaterials,2009,30(29):5892-5896
[237] B. Romberg, W. Hennink, G. Storm, Sheddable Coatings for Long-CirculatingNanoparticles. Pharm Res-Dordr,2008,25(1):55-71
[238] H. Hatakeyama, H. Akita, K. Kogure, et al, Development of a novel systemic gene deliverysystem for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Therapy,2006,14(1):68-77
[239] C. Clawson, L. Ton, S. Aryal, et al, Synthesis and Characterization of Lipid-Polymer HybridNanoparticles with pH-Triggered Poly(ethylene glycol) Shedding. Langmuir,2011,27(17):10556-10561
[240] A. Soderberg, B. Sahaf, A. Rosen, Thioredoxin reductase, a redox-active selenoprotein, issecreted by normal and neoplastic cells: Presence in human plasmal. Cancer Res,2000,60(8):2281-2289
[241] T. B. Ren, W. J. Xia, H. Q. Dong, et al, Sheddable micelles based on disulfide-linked hybridPEG-polypeptide copolymer for intracellular drug delivery. Polymer,2011,52(16):3580-3586
[242] Y. Luk, M. Kato, M. Mrksich, Self-Assembled Monolayers of Alkanethiolates PresentingMannitol Groups Are Inert to Protein Adsorption and Cell Attachment. Langmuir,2000,16(24):9604-9608
[243] N. V. Efremova, S. R. Sheth, D. E. Leckband, Protein-Induced Changes in Poly(ethyleneglycol) Brushes: Molecular Weight and Temperature Dependence. Langmuir,2001,17(24):7628-7636
[244] P. S. Xu, G. Bajaj, T. Shugg, et al, Zwitterionic Chitosan Derivatives for pH-SensitiveStealth Coating. Biomacromolecules,2010,11(9):2352-2358
[245] M. E. Napier, J. M. Desimone, Nanoparticle drug delivery platform. Polymer Reviews,2007,47(3):321-327
[246] S. R. Mudshinge, A. B. Deore, S. Patil, et al, Nanoparticles: Emerging carriers for drugdelivery. Saudi Pharm J,2011,19(3):129-141
[247] A. S. Mikhail, C. Allen, Block copolymer micelles for delivery of cancer therapy: Transportat the whole body, tissue and cellular levels. J Control Release,2009,138(3):214-223
[248] M. C. Jones, J. C. Leroux, Polymeric micelles-a new generation of colloidal drug carriers.European Journal of Pharmaceutics and Biopharmaceutics,1999,48(2):101-111
[249] Y. Q. Shen, E. L. Jin, B. Zhang, et al, Prodrugs Forming High Drug LoadingMultifunctional Nanocapsules for Intracellular Cancer Drug Delivery. J Am Chem Soc,2010,132(12):4259-4265
[250] L. Bildstein, C. Dubernet, P. Couvreur, Prodrug-based intracellular delivery of anticanceragents. Adv Drug Deliver Rev,2011,63(1-2):3-23
[251] G. L. Li, J. Y. Liu, Y. Pang, et al, Polymeric Micelles with Water-Insoluble Drug asHydrophobic Moiety for Drug Delivery. Biomacromolecules,2011,12(6):2016-2026
[252] J. A. MacKay, M. N. Chen, J. R. McDaniel, et al, Self-assembling chimericpolypeptide-doxorubicin conjugate nanoparticles that abolish tumours after a single injection.Nature Materials,2009,8(12):993-999
[253] H. S. Yoo, T. G. Park, Folate-receptor-targeted delivery of doxorubicin nano-aggregatesstabilized by doxorubicin-PEG-folate conjugate. J Control Release,2004,100(2):247-256
[254] G. Y. Lee, K. Park, S. Y. Kim, et al, MMPs-specific PEGylated peptide-DOX conjugatemicelles that can contain free doxorubicin. European Journal of Pharmaceutics andBiopharmaceutics,2007,67:646-654
[255] A. S. Mikhail, C. Allen, Poly(ethylene glycol)-b-poly(epsilon-caprolactone) MicellesContaining Chemically Conjugated and Physically Entrapped Docetaxel: Synthesis,Characterization, and the Influence of the Drug on Micelle Morphology. Biomacromolecules,2010,11(5):1273-1280
[256] S. Fukushima, M. Machida, T. Akutsu, et al, Roles of adriamycin and adriamycin dimer inantitumor activity of the polymeric micelle carrier system. Colloid Surface B,1999,16(1-4):227-236
[257] T. Nakanishi, S. Fukushima, K. Okamoto, et al, Development of the polymer micelle carriersystem for doxorubicin. J Control Release,2001,74(1-3):295-302
[258] L. Zhou, R. Cheng, H. Tao, et al, Endosomal pH-Activatable Poly(ethyleneoxide)-graft-Doxorubicin Prodrugs: Synthesis, Drug Release, and Biodistribution inTumor-Bearing Mice. Biomacromolecules,2011,12(5)
[259] M. Hruby, C. Konak, K. Ulbrich, Polymeric micellar pH-sensitive drug delivery system fordoxorubicin. J Control Release,2005,103(1):137-148
[260] T. B. Ren, Y. Feng, H. Q. Dong, et al, Sheddable Nanoparticles for Biomedical Application.Progress in Chemistry,2011,23(1):213-220
[261] H. Cheng, J. L. Zhu, X. Zeng, et al, Targeted Gene Delivery Mediated byFolate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity. BioconjugateChem,2009,20(3):481-487
[262] A. S. Hoffman, Hydrogels for biomedical applications. Ann Ny Acad Sci,2001,944:62-73