癌症诊治用纳米硅质体的制备及功能研究
|
摘要
癌症是威胁人类健康和生存的重大疾病，长期以来，广大科研人员不断探索和开发各种各样的治疗方法，药物载体是其中重要的一方面，因为它可以有效地防止药物降解，将药物输送到病变区域，降低毒副作用，提高治疗效果。然而，随着时代的发展，传统药物载体逐渐暴露出了一些缺点，如稳定性差、生物相容性差、载药量低、肿瘤靶向富集少、体内循环时间短等，这些问题极大地降低了药物的生物利用度，增加了患者的痛苦，因此，迫切需要发展新型药物载体。当前，药物载体正向着可控化、智能化、绿色化和诊疗一体化的方向发展，不断涌现出了各种具有良好发展前景的新型载体。有机-无机复合载体材料就是其中的一种，它综合了有机物和无机物的特性，具备独特的优势。本文以有机无机复合材料的一种——硅质体作为研究对象，从有机-无机复合脂质分子设计的角度出发，在药物载体的结构控制释放、光控释放、光动力治疗，以及光动力治疗结合磁共振成像等方面开展了系统的研究。
研究了有机无机复合脂质结构对硅质体药物释放性能的影响。通过调节脂质分子亲疏水基团的比例，合成了4种不同结构的复合脂质分子，利用溶胶凝胶和自组装技术获得了四种具有不同表层硅酸盐网络致密度的新型硅质体，并以亲水药物阿霉素和疏水药物紫杉醇为代表，成功制备了4种阿霉素硅质体和4种紫杉醇硅质体。通过体外药物释放行为和细胞毒性的对比分析，阐明了载体对药物的释放性能与相应复合脂质的结构密切相关。实验结果表明，各载体对药物均具有良好的缓释作用，当疏水基团相同时，亲水硅烷数量越多，药物的释放速率越慢；当亲水硅烷相同时，疏水基团越多，对亲水药物的释放越快，而对疏水药物的释放则越慢。细胞实验结果表明，各载药硅质体对细胞的抑制作用与其药物释放行为一致，即载体对药物的释放越快，则相同药物浓度和相同孵育时间下对细胞的抑制作用也越明显，充分体现了分子结构的设计对脂质双层渗透性的有效调控。
开展了高度稳定灵敏的光响应控制释药载体材料的研究。通过有机合成的方法将光敏感基团偶氮苯与复合脂质相结合，获得了一种新型的光响应有机无机复合脂质分子，进而制备了脂质双层富含偶氮苯基团的光响应囊泡载体。通过紫外可见吸收光谱研究了囊泡中偶氮苯基团光致异构的情况，阐明了光致异构的影响因素。实验结果表明，脂质双层中偶氮苯基团与脂质双链主要以交替排列的方式分布，在紫外光和可见光轮流照射下，双层中的偶氮苯能顺利地实现可逆的构型异构，且其反-顺异构化比例可达到33.4%。以染料尼罗红作为模型药物，研究了光响应载体的光控释药性能。研究发现，在紫外光照下，载体在20min内即可释放48.2%的尼罗红，表现出灵敏的光响应控制释药能力。
研制了具有光动力治疗和荧光诊断功能的硅质体。将卟啉基团引入复合脂质分子中，合成了含有双链、硅烷头部、卟啉基团的新型复合脂质，制备了相应的卟啉硅质体光动力载体材料，其光敏剂载药量可高达33.4%。通过包载亲水性染料钙黄绿素研究了卟啉硅质体的囊泡结构；通过大量的实验和讨论分析，研究了载体双层中卟啉基团的聚集和排列方式、化学共价键连卟啉基团的重要作用、单线态氧产生的情况并解释了其产生机理，探讨载体被细胞摄取的方式，并通过细胞形态变化和MTT方法研究了光动力治疗效果，在此基础上进行了初步的动物实验，考察载体在大鼠血液中的循环动力学。实验结果表明，卟啉硅质体脂质双层中卟啉基团基本不存在聚集情况，其与双链之间主要以交替方式有序排列，在紫外光照射下，载体呈现出明显的红色荧光。在重水和细胞中卟啉硅质体均能显著地产生单线态氧，且产生效率与浓度和时间成正比。激光共聚焦显微镜图片清楚地显示载体以内吞方式被肿瘤细胞摄取，且主要聚集于溶酶体中。载体对细胞表现出很低的暗毒性和显著高的光毒性，且在血液中具有长循环的特点，体现了其作为药物载体的显著优势。
构建了同时具有磁共振成像与光动力治疗功能的诊疗一体化纳米粒子。在前一章合成的基础上，将卟啉与金属锰卟啉衍生物相结合，制备了一种内有双层卟啉基团外有金属锰卟啉的新型纳米粒子，其中脂质双层中的卟啉用于光动力治疗，外层的锰卟啉用于磁共振成像。研究了该类粒子的制备方法、光谱性质、单线态氧产生效率、细胞摄取实验，并在此基础上进行体外磁共振成像效果和光动力治疗效果的检测。实验结果表明，所制备的纳米粒子在透射电镜下呈现明显的核壳结构，通过调节5种不同比例的外层锰卟啉，可制备出光动力治疗和磁共振成像效果可调节的纳米粒子，随着键连锰卟啉比例的增加，粒子对水质子的纵向驰豫效率加速也越明显，达到40.1%以上时，成像效果达到最佳。细胞实验证实了该纳米粒子能被肿瘤细胞有效摄取，且对细胞具有低暗毒性和高光毒性，最终能同时满足成像和光动力治疗的纳米粒子上键连锰卟啉的最佳比例是40.1%。
Cancer is a threat disease to human health and survival, for a long time, themajority of researchers have been continuing to explore and develop a variety oftreatment methods, drug delivery is an important one, because it can effectivelyprevent drug degradation, transport drug to the lesions, reduce toxicity and increasetherapeutic effect. However, with the development of the times, the traditional drugcarriers gradually revealed some shortcomings, such as poor stability, poorbiocompatibility, low drug loading efficiency, less enrichment in targeting tumor andshort circulation time in vivo, these problems greatly reduce the bioavailability ofdrug and increase the suffering of patients, therefore, there is an urgent need todevelop new drug carriers. Currently, the drug carrier is toward in the direction ofcontrolled, intelligent, green and theranostic, developing a variety of new carrierswith good prospects. Organic-inorganic hybrid material is one of them, whichcombines the characteristics of organic and inorganic materials, possessing uniqueadvantages. In this paper, an organic-inorganic hybrid materials–Cerasome wasused as the main object of study, with the view point of molecular design for theorganic-inorganic hybrid lipid, systematic research in the structure-controlledrelease, light-controlled release, photodynamic therapy, and photodynamic therapycombined with magnetic resonance imaging were carried out.
The relationship between the hybrid lipid structure and drug release properties ofCerasome was researched. By adjusting the ratio of hydrophilic and hydrophobicgroups in the lipid molecules, four lipids with different structures were synthesized,later sol-gel and self-assembly technologies were applied to obtain four newCerasomes with silicate network of different surface density. Hydrophilic drugdoxorubicin and hydrophobic drug paclitaxel were used as the model drug, four kindsof doxorubicin-Cerasomes and paclitaxel-Cerasomes were successfully prepared. Invitro drug release behavior and cytotoxicity results showed that the release propertiesof drug carriers were closely related with structure of the corresponding lipids. Allthe carriers can release the drug slowly, with the same hydrophobic groups, thehigher number of hydrophilic silane group, the slower release rate of the drug. Incontrast, with the same hydrophilic silane groups, the more the hydrophobic groupresulted in the faster release rate of hydrophilic drug and the slower release for thehydrophobic drug. Cell experiments showed that the inhibition effect of the drugloaded Cerasomes were consistent with their drug release behavior, that is to say,with the same drug concentration and incubation time, the faster drug release from the carriers lead to more obvious inhibitory effect on cells. These results fully reflectthe design of the molecular structure can effectively regulate the permeability of theCerasome bilayer.
Highly stable and sensitive light-responsive material for controlled drug releasehad been studied. Photosensitive azobenzene group was introduced into the hybridlipid by organic synthesis to obtained a new type of photoresponsive organic-inorganic hybrid lipid, thus light-responsive vesicle with azobenzene lipid bilayerwas prepared. Photo-isomerization of the azobenzene unit in the vesicles wasdetected by UV-visible absorption spectra, affecting factors to the photo-isomerization was clarified. The results showed that the azobenzene group anddouble-chain were mainly distributed in the vesicle bilayer with an alternative mode.With alternative irradiation by UV and visible light, the azobenzene group canachieve a reversible configuration conversion, and its trans-isomerization ratio was33.4%. Nile red was use as a model drug to study the photo controlled-releaseperformance of the carrier. The study found that upon UV light irradiation, the carriercan released Nile red of48.2%in20min, showing the sensitive capabilities of light-controlled drug release.
Cerasome with fluorescence and photodynamic function was developed. Theintroduction of the porphyrin groups to the hybrid lipid resulted in a new hybrid lipidcontaining double-chain, porphyrin and silane head groups, the correspondingporphyrin Cerasome used as photodynamic agents were then prepared, its drug-loaded efficiency could reach to33.4%. The vesicular structure of porphyrinCerasome was verified by encapsulation a hydrophilic dye of calcein. A lot ofexperiments combined with discussion and analysis were carried out to study theaggregation and arrangement mode of the porphyrin groups, the important role ofchemical covalent bonded with porphyrin groups, singlet oxygen generatedefficiency and mechanism, and cellular uptaken way. Observation on cellmorphology and MTT assay were applied to test the photodynamic effect, finallypreliminary animal experiments were carried out to study the blood circulationdynamics of the carrier in rat. The results showed that double-chain and porphyrinunit should mainly arrange in an orderly alternating manner, so aggregation ofporphyrin unit in the Cerasome did not exist, upon UV light irradiation, the carriershowed brightly red fluorescence. Porphyrin Cerasome can significantly generatedsinglet oxygen in heavy water and cancer cells, and singlet oxygen generatedefficiency was proportional to the carrier concentration and light irradiating time.Confocal laser scanning microscopy images clearly showed porphyrin Cerasome wasuptaken by tumor cells through an endocytosis way, and mainly located in the lysosome. The vesicle exhibited low dark toxicity and significant phototoxicity to thecells, and it could maintain a long circulating time in the blood, showing thesignificant advantage as drug carrier.
Theranostic nanoparticle simultaneously with photodynamic therapy and magneticresonance imaging abilities was design and prepared. Based on the synthesis in theprevious chapter, the porphyrin and manganese porphyrin derivatives were combinedtogether to obtain a new kind of nanoparticles with inside double-porphyrin bilayerand outside manganese porphyrin, in which inside porphyrin was for photodynamictherapy, the outer layer of manganese porphyrin was for magnetic resonance imaging.Studies for such particles were carried out, including preparation method,spectroscopic properties, singlet oxygen generated efficiency, cellular uptaken, invitro magnetic resonance imaging and photodynamic therapy testing. Experimentalresults showed that the nanoparticles showed obvious core-shell structure in TEM.By adjusting the ratio of the outer manganese porphyrins, five different nanoparticleswith adjustable photodynamic effect and magnetic resonance imaging can beprepared. The more proportion of manganese porphyrin led to the higher acceleratedlongitudinal relaxation efficiency of water proton, the ratio of higher than40.1%canresulted in the best imaging results. Cell experiments confirmed that thenanoparticles can be effectively uptaken by tumor cells and showed low dark toxicityand high phototoxicity, the ultimate nanoparticles to meet the imaging andphotodynamic therapy effect was the one with manganese porphyrins ratio of40.1%.
研究了有机无机复合脂质结构对硅质体药物释放性能的影响。通过调节脂质分子亲疏水基团的比例，合成了4种不同结构的复合脂质分子，利用溶胶凝胶和自组装技术获得了四种具有不同表层硅酸盐网络致密度的新型硅质体，并以亲水药物阿霉素和疏水药物紫杉醇为代表，成功制备了4种阿霉素硅质体和4种紫杉醇硅质体。通过体外药物释放行为和细胞毒性的对比分析，阐明了载体对药物的释放性能与相应复合脂质的结构密切相关。实验结果表明，各载体对药物均具有良好的缓释作用，当疏水基团相同时，亲水硅烷数量越多，药物的释放速率越慢；当亲水硅烷相同时，疏水基团越多，对亲水药物的释放越快，而对疏水药物的释放则越慢。细胞实验结果表明，各载药硅质体对细胞的抑制作用与其药物释放行为一致，即载体对药物的释放越快，则相同药物浓度和相同孵育时间下对细胞的抑制作用也越明显，充分体现了分子结构的设计对脂质双层渗透性的有效调控。
开展了高度稳定灵敏的光响应控制释药载体材料的研究。通过有机合成的方法将光敏感基团偶氮苯与复合脂质相结合，获得了一种新型的光响应有机无机复合脂质分子，进而制备了脂质双层富含偶氮苯基团的光响应囊泡载体。通过紫外可见吸收光谱研究了囊泡中偶氮苯基团光致异构的情况，阐明了光致异构的影响因素。实验结果表明，脂质双层中偶氮苯基团与脂质双链主要以交替排列的方式分布，在紫外光和可见光轮流照射下，双层中的偶氮苯能顺利地实现可逆的构型异构，且其反-顺异构化比例可达到33.4%。以染料尼罗红作为模型药物，研究了光响应载体的光控释药性能。研究发现，在紫外光照下，载体在20min内即可释放48.2%的尼罗红，表现出灵敏的光响应控制释药能力。
研制了具有光动力治疗和荧光诊断功能的硅质体。将卟啉基团引入复合脂质分子中，合成了含有双链、硅烷头部、卟啉基团的新型复合脂质，制备了相应的卟啉硅质体光动力载体材料，其光敏剂载药量可高达33.4%。通过包载亲水性染料钙黄绿素研究了卟啉硅质体的囊泡结构；通过大量的实验和讨论分析，研究了载体双层中卟啉基团的聚集和排列方式、化学共价键连卟啉基团的重要作用、单线态氧产生的情况并解释了其产生机理，探讨载体被细胞摄取的方式，并通过细胞形态变化和MTT方法研究了光动力治疗效果，在此基础上进行了初步的动物实验，考察载体在大鼠血液中的循环动力学。实验结果表明，卟啉硅质体脂质双层中卟啉基团基本不存在聚集情况，其与双链之间主要以交替方式有序排列，在紫外光照射下，载体呈现出明显的红色荧光。在重水和细胞中卟啉硅质体均能显著地产生单线态氧，且产生效率与浓度和时间成正比。激光共聚焦显微镜图片清楚地显示载体以内吞方式被肿瘤细胞摄取，且主要聚集于溶酶体中。载体对细胞表现出很低的暗毒性和显著高的光毒性，且在血液中具有长循环的特点，体现了其作为药物载体的显著优势。
构建了同时具有磁共振成像与光动力治疗功能的诊疗一体化纳米粒子。在前一章合成的基础上，将卟啉与金属锰卟啉衍生物相结合，制备了一种内有双层卟啉基团外有金属锰卟啉的新型纳米粒子，其中脂质双层中的卟啉用于光动力治疗，外层的锰卟啉用于磁共振成像。研究了该类粒子的制备方法、光谱性质、单线态氧产生效率、细胞摄取实验，并在此基础上进行体外磁共振成像效果和光动力治疗效果的检测。实验结果表明，所制备的纳米粒子在透射电镜下呈现明显的核壳结构，通过调节5种不同比例的外层锰卟啉，可制备出光动力治疗和磁共振成像效果可调节的纳米粒子，随着键连锰卟啉比例的增加，粒子对水质子的纵向驰豫效率加速也越明显，达到40.1%以上时，成像效果达到最佳。细胞实验证实了该纳米粒子能被肿瘤细胞有效摄取，且对细胞具有低暗毒性和高光毒性，最终能同时满足成像和光动力治疗的纳米粒子上键连锰卟啉的最佳比例是40.1%。
Cancer is a threat disease to human health and survival, for a long time, themajority of researchers have been continuing to explore and develop a variety oftreatment methods, drug delivery is an important one, because it can effectivelyprevent drug degradation, transport drug to the lesions, reduce toxicity and increasetherapeutic effect. However, with the development of the times, the traditional drugcarriers gradually revealed some shortcomings, such as poor stability, poorbiocompatibility, low drug loading efficiency, less enrichment in targeting tumor andshort circulation time in vivo, these problems greatly reduce the bioavailability ofdrug and increase the suffering of patients, therefore, there is an urgent need todevelop new drug carriers. Currently, the drug carrier is toward in the direction ofcontrolled, intelligent, green and theranostic, developing a variety of new carrierswith good prospects. Organic-inorganic hybrid material is one of them, whichcombines the characteristics of organic and inorganic materials, possessing uniqueadvantages. In this paper, an organic-inorganic hybrid materials–Cerasome wasused as the main object of study, with the view point of molecular design for theorganic-inorganic hybrid lipid, systematic research in the structure-controlledrelease, light-controlled release, photodynamic therapy, and photodynamic therapycombined with magnetic resonance imaging were carried out.
The relationship between the hybrid lipid structure and drug release properties ofCerasome was researched. By adjusting the ratio of hydrophilic and hydrophobicgroups in the lipid molecules, four lipids with different structures were synthesized,later sol-gel and self-assembly technologies were applied to obtain four newCerasomes with silicate network of different surface density. Hydrophilic drugdoxorubicin and hydrophobic drug paclitaxel were used as the model drug, four kindsof doxorubicin-Cerasomes and paclitaxel-Cerasomes were successfully prepared. Invitro drug release behavior and cytotoxicity results showed that the release propertiesof drug carriers were closely related with structure of the corresponding lipids. Allthe carriers can release the drug slowly, with the same hydrophobic groups, thehigher number of hydrophilic silane group, the slower release rate of the drug. Incontrast, with the same hydrophilic silane groups, the more the hydrophobic groupresulted in the faster release rate of hydrophilic drug and the slower release for thehydrophobic drug. Cell experiments showed that the inhibition effect of the drugloaded Cerasomes were consistent with their drug release behavior, that is to say,with the same drug concentration and incubation time, the faster drug release from the carriers lead to more obvious inhibitory effect on cells. These results fully reflectthe design of the molecular structure can effectively regulate the permeability of theCerasome bilayer.
Highly stable and sensitive light-responsive material for controlled drug releasehad been studied. Photosensitive azobenzene group was introduced into the hybridlipid by organic synthesis to obtained a new type of photoresponsive organic-inorganic hybrid lipid, thus light-responsive vesicle with azobenzene lipid bilayerwas prepared. Photo-isomerization of the azobenzene unit in the vesicles wasdetected by UV-visible absorption spectra, affecting factors to the photo-isomerization was clarified. The results showed that the azobenzene group anddouble-chain were mainly distributed in the vesicle bilayer with an alternative mode.With alternative irradiation by UV and visible light, the azobenzene group canachieve a reversible configuration conversion, and its trans-isomerization ratio was33.4%. Nile red was use as a model drug to study the photo controlled-releaseperformance of the carrier. The study found that upon UV light irradiation, the carriercan released Nile red of48.2%in20min, showing the sensitive capabilities of light-controlled drug release.
Cerasome with fluorescence and photodynamic function was developed. Theintroduction of the porphyrin groups to the hybrid lipid resulted in a new hybrid lipidcontaining double-chain, porphyrin and silane head groups, the correspondingporphyrin Cerasome used as photodynamic agents were then prepared, its drug-loaded efficiency could reach to33.4%. The vesicular structure of porphyrinCerasome was verified by encapsulation a hydrophilic dye of calcein. A lot ofexperiments combined with discussion and analysis were carried out to study theaggregation and arrangement mode of the porphyrin groups, the important role ofchemical covalent bonded with porphyrin groups, singlet oxygen generatedefficiency and mechanism, and cellular uptaken way. Observation on cellmorphology and MTT assay were applied to test the photodynamic effect, finallypreliminary animal experiments were carried out to study the blood circulationdynamics of the carrier in rat. The results showed that double-chain and porphyrinunit should mainly arrange in an orderly alternating manner, so aggregation ofporphyrin unit in the Cerasome did not exist, upon UV light irradiation, the carriershowed brightly red fluorescence. Porphyrin Cerasome can significantly generatedsinglet oxygen in heavy water and cancer cells, and singlet oxygen generatedefficiency was proportional to the carrier concentration and light irradiating time.Confocal laser scanning microscopy images clearly showed porphyrin Cerasome wasuptaken by tumor cells through an endocytosis way, and mainly located in the lysosome. The vesicle exhibited low dark toxicity and significant phototoxicity to thecells, and it could maintain a long circulating time in the blood, showing thesignificant advantage as drug carrier.
Theranostic nanoparticle simultaneously with photodynamic therapy and magneticresonance imaging abilities was design and prepared. Based on the synthesis in theprevious chapter, the porphyrin and manganese porphyrin derivatives were combinedtogether to obtain a new kind of nanoparticles with inside double-porphyrin bilayerand outside manganese porphyrin, in which inside porphyrin was for photodynamictherapy, the outer layer of manganese porphyrin was for magnetic resonance imaging.Studies for such particles were carried out, including preparation method,spectroscopic properties, singlet oxygen generated efficiency, cellular uptaken, invitro magnetic resonance imaging and photodynamic therapy testing. Experimentalresults showed that the nanoparticles showed obvious core-shell structure in TEM.By adjusting the ratio of the outer manganese porphyrins, five different nanoparticleswith adjustable photodynamic effect and magnetic resonance imaging can beprepared. The more proportion of manganese porphyrin led to the higher acceleratedlongitudinal relaxation efficiency of water proton, the ratio of higher than40.1%canresulted in the best imaging results. Cell experiments confirmed that thenanoparticles can be effectively uptaken by tumor cells and showed low dark toxicityand high phototoxicity, the ultimate nanoparticles to meet the imaging andphotodynamic therapy effect was the one with manganese porphyrins ratio of40.1%.
引文
[1] Singh A K, Pandey A, R. Rai, et al. Nanomaterials as Emerging Tool in CancerDiagnosis and Treatment[J]. Digest Journal of Nanomaterials and Biostructures,2008,3（3）：135-140.
[2] Charman W N, Chan H-K, Finnin B C，et al. Drug Delivery: A Key Factor inRealising the Full Therapeutic Potential of Drugs[J]. Drug DevelopmentResearch,1999,46（3-4）：316-327.
[3] Kopecek J. Smart and Genetically Engineered Biomaterials and Drug DeliverySystems[J]. European Journal of Pharmaceutical Sciences,2003,20（1）：1-16.
[4] Torchilin V P. Structure and Design of Polymeric Surfactant-Based DrugDelivery Systems[J]. Journal of Controlled Release,2001,73（2-3）：137-172.
[5] Bergh J. Quo Vadis with Targeted Drugs in the21st Century[J]? Journal ofClinical Oncology,2009,27（1）：2-5.
[6] Fojo T, Grady C. How Much is Life Worth: Cetuximab, Non-Small Cell LungCancer, and the$440Billion Question[J]. Journal of the National CancerInstitute,2009,101（15）：1044-1048.
[7] Hampton T. Targeted Cancer Therapies Lagging: Better Trial Design CouldBoost Success Rate[J]. Journal of the American Medical Association,2006,296（16）：1951-1952.
[8] Rai A J, Yee J, Fleisher M. Biomarkers in the Era of Personalized Medicine-aMultiplexed SNP Assay Using Capillary Electrophoresis for Assessing DrugMetabolism Capacity[J]. Scandinavian Journal of Clinical and LaboratoryInvestigation,2010,70（242）：15-18.
[9] Blanchet K D. Redefining Personalized Medicine in the Postgenomic Era:Developing Bladder Cancer Therapeutics with Proteomics[J]. British Journal ofUrology International,2010,105（2）：i-iii.
[10] Francke U. On the Bumpy Road Towards ‘Personalized Medicine’[J]. EMBOMolecular Medicine,2010,2（1）：1-2.
[11] Bates S. Progress Towards Personalized Medicine[J]. Drug Discovery Today,2010,15（3-4）：115-120.
[12] Espina V, Liotta L A, Petricoin III E F. Reverse-Phase Protein Microarrays forTheranostics and Patient Tailored Therapy[J]. Methods in Molecular Biology,2009,520：89-105.
[13] Falk J. Epigenetics&Sequencing-Gene Expression Systems' SecondInternational Meeting. Chromatin Methylation to Disease Biology&Theranostics[J]. Idrugs,2008,11（9）：650-652.
[14] Muller-Goymann C C. Physicochemical Characterization of Colloidal DrugDelivery Systems such as Reverse Micelles, Vesicles, Liquid Crystals AndNanoparticles for Topical Administration[J]. European Journal ofPharmaceutics and Biopharmaceutics,2004,58（2）：343-356.
[15] Haag R. Supramolecular Drug-Delivery Systems Based on Polymeric Core-Shell Architectures[J]. Angewandte Chemie International Edition,2004,43（3）：278-282.
[16] Gaucher G, Dufresne M-H, Sant V P, et al. Block Copolymer Micelles:Preparation, Characterization and Application in Drug Delivery[J]. Journal ofControlled Release,2005,109（1-3）：169-188.
[17] Nallamothu R, Wood G C, Pattillo C B, et al. A Tumor Vasculature TargetedLiposome Delivery System for Combretastatin A4: Design, Characterization,and in Vitro Evaluation[J]. AAPS Pharmscitech,2006,7（2）：E1-E10.
[18] Pal K, Banthia A K, Majumdar D K. Polymeric Hydrogels: Characterization andBiomedical Applications[J]. Designed Monomers and Polymers,2009,12（3）：197-220.
[19] Huo Q, Margolese D I, Stucky G D. Surfactant Control of Phases in theSynthesis of Mesoporous Silica-Based Materials[J]. Chemistry of Materials,1996,8（5）：1147-1160.
[20] Shimojima A, Sugahara Y, Kuroda K. Inorganic-Organic Layered MaterialsDerived Via the Hydrolysis and Polycondensation of Trialkoxy(Alkyl)Silanes[J].Bulletin of the Chemical Society of Japan,1997,70（11）：2847-2853.
[21] Moreau J J E, Vellutini L, Man M W C, et al. Self-Organized Hybrid Silica withLong-Range Ordered Lamellar Structure[J]. Journal of the American ChemicalSociety,2001,123（32）：7957-7958.
[22] Ruiz-Hitzky E, Letaief S, Prévot V. Novel Organic-Inorganic Mesophases: Self-templating Synthesis and Intratubular Swelling[J]. Advanced Materials,2002,14（6）：439-443.
[23] Zhang Q, Ariga K, Okabe A, et al. A Condensable Amphiphile with a CleavableTail as a “Lizard” Template for the Sol Gel Synthesis of FunctionalizedMesoporous Silica[J]. Journal of the American Chemical Society,2004,126（4）：988-989.
[24] Katagiri K, Ariga K, Kikuchi J. Preparation of Organic-Inorganic Hybrid Vesicle"Cerasome" Derived from Artificial Lipid with Alkoxysilyl Head[J]. ChemistryLetters,1999,（7）：661-662.
[25] Kunitake T. Synthetic Bilayer Membranes: Molecular Design, Self-Organization,and Application[J]. Angewandte Chemie International Edition,1992,31（6）：709-726.
[26] Israelachivili J N, Mitchell D J, Ninham B W. Theory of Self-Assembly ofHydrocarbon Amphiphiles into Micelles and Bilayers[J]. Journal of theChemical Society, Faraday Transactions,1976,72：1525-1568.
[27] Hashizume M, Kawanami S, Iwamoto S, et al. Stable Vesicular Nanoparticle“Cerasome” as an Organic-Inorganic Hybrid Formed with OrganoalkoxysilaneLipids Having a Hydrogen-Bonding Unit[C]. Thin Solid Films,2003,438-439：20-26.
[28] Katagiri K, Hamasaki R, Ariga K, et al. Layered Paving of VesicularNanoparticles Formed with Cerasome as a Bioinspired Organic-InorganicHybrid[J]. Journal of the American Chemical Society,2002,124（27）：7892-7893.
[29] Sasaki Y, Matsui K, Aoyama Y, et al. Cerasome as an infusible and Cell friendlyGene Carrier: Synthesis of Cerasome-forming Lipids and Transfection usingCerasome[J]. Nature Protocols,2006,1（3）：1227-1234.
[30] Hashizume M, Inoue H, Katagiri K, et al. Cerasome as an Organic-Inorganicvesicular Nanohybrid. Characterization of Cerasome-forming Lipids Having aSingle or a Dual Trialkoxysilyl Head[C]. Journal of Sol-Gel Science andTechnology,2004,31（1-3）：99-102.
[31] Katagiri K, Hashizume M, Ariga K, et al. Preparation and Characterization of aNovel Organic-Inorganic Nanohybrid "Cerasome" formed with a LiposomalMembrane and Silicate Surface[J]. Chemistry-A European Journal,2007,13（18）：5272-5281.
[32] Ariga K, Katagiri K, Kikuchi J. Preparation Condition of a Novel Organic-Inorganic Hybrid Vesicle “Cerasome”[J]. Kobunshi Ronbunshu,2000,57（4）：251-253.
[33] Katagiri K, Ariga K, Kikuchi J. Novel Class of Organic-Inorganic HybridVesicle “Cerasome” Derived from various Amphiphiles with AlkoxysilylHead[J]. Studies in Surface Science and Catalysis,2001,132：599-602.
[34] Katagiri K, Hamasaki R, Ariga K, et al. Preparation and Surface Modification ofNovel Vesicular Nano-Particle “Cerasome” with Liposomal Bilayer and SilicateSurface[C]. Journal of Sol-Gel Science and Technology,2003,26（1-3）：393-396.
[35] Cao Z, Ma Y, Yue X, et al. Stabilized Liposomal Nanohybrid Cerasomes forDrug Delivery Applications[J]. Chemical Communications,2010,46（29）：5265-5267.
[36] Sasaki Y, Yamada M, Terashima T, et al. Construction of IntermolecularCommunication System on “Cerasome” as an Organic-Inorganic Nanohybrid[J].Kobunshi Ronbunshu,2004,61（10）：541-546.
[37] Katagiri K, Hamasaki R, Ariga K, et al. Layer-by-layer Self-Assembling ofLiposomal Nanohybrid “Cerasome” on Substrates[J]. Langmuir,2002,18（17）：6709-6711.
[38] Katagiri K, Hamasaki R, Hashizume M, et al. Size-Selective Organization ofSilica and Silica-Like Particles on Solid Interfaces through Layer-by-layerAssembly[C]. Journal of Sol-Gel Science and Technology,2004,31（1-3）：59-62.
[39] Matsui K, Sasaki Y, Komatsu T, et al. RNAi Gene Silencing Using Cerasome asa Viral-Size siRNA-Carrier free from Fusion and Crosslinking[J]. Bioorganic&Medicinal Chemistry Letters,2007,17（14）：3935-3938.
[40] Hashizume M, Sasaki Y, Terashima T, et al. Creation of Organized Assembly ofCerasomes on DNA Templates[J]. Kobunshi Ronbunshu,2008,65（6）：421-426.
[41] Kabanov A V, Kabanov V A. DNA Complexes with Polycations for the Deliveryof Genetic Material into Cells[J]. Bioconjugate Chemistry,1995,6（1）：7-20.
[42] Mintzer M A, Simanek E E. Nonviral Vectors for Gene Delivery[J]. ChemicalReviews,2009,109（2）：259-302.
[43] Matsui K, Sando S, Sera T, et al. Cerasome as an Infusible, Cell-Friendly, andSerum-Compatible Transfection Agent in a Viral Size[J]. Journal of theAmerican Chemical Society,2006,128（10）：3114-3115.
[44] Vauthier C, Labarre D. Modular Biomimetic Drug. Delivery Systems[J]. Journalof Drug Delivery Science&Technology,2008,18（1）：59-68.
[45] Bayer C L, Peppas N A. Advances in Recognitive, Conductive and ResponsiveDelivery Systems[J]. Journal of Controlled Release,2008,132（3）：216-221.
[46] Youan B B C. Chronopharmaceutics: Gimmick or Clinically Relevant Approachto Drug Delivery[J]? Journal of Controlled Release,2004,98（3）：337-353.
[47] Alvarez-Lorenzo C, Concheiro A. Intelligent Drug Delivery Systems: PolymericMicelles and Hydrogels[J]. Mini-Reviews in Medicinal Chemistry,2008,8（11）：1065-1074.
[48] Anil A K. Stimuli-Induced Pulsatile or Triggered Release Delivery Systems forBioactive Compounds. Recent Pat. Endocr., Metab[P]. Immune Drug Discovery,2007,1：83-90.
[49] Kost J, Langer R. Responsive Polymeric Delivery Systems[J]. Advanced DrugDelivery Reviews,2001,46（1-3）：125-148.
[50] Sershen S, Wes J. Implantable, Polymeric Systems for Modulated DrugDelivery[J]. Advanced Drug Delivery Reviews,2002,54（9）：1225-1235.
[51] Qiu Y, Park K. Environment-Sensitive Hydrogels for Drug Delivery[J].Advanced Drug Delivery Reviews,2001,53（3）：321-339.
[52] Murdan S. Electro-Responsive Drug Delivery from Hydrogels[J]. Journal ofControlled Release,2003,92（1-2）：1-17.
[53] Sunil A, Kulkarni R V, Mallikarjuna N N, et al. Electrically ModulatedTransport of Diclofenac Salts Through Hydrogels of Sodium Alginate, Carbopol,and Their Blend Polymers[C]. Journal of Applied Polymer Science,2005,96（2）：301-311.
[54] Rapoport N. Physical Stimuli-Responsive Polymeric Micelles for Anti-CancerDrug Delivery[J]. Progress in Polymer Science,2007,32（8-9）：962-990.
[55] Andresen T L, Jensen S S, Jorgensen K. Advanced Strategies in LiposomalCancer Therapy: Problems and Prospects of Active and Tumor Specific DrugRelease[J]. Progress in Lipid Research,2005,44（1）：68-97.
[56] Chung C M, Roh Y S, Cho S Y, et al. Crack Healing in Polymeric Materials ViaPhotochemical [2+2] Cycloaddition[J]. Chemistry of Materials,2004,16（21）：3982-3984.
[57] Wu D Y, Meure S, Solomon D. Self-Healing Polymeric Materials: a Review ofRecent Developments[J]. Progress in Polymer Science,2008,33（5）：479-522.
[58] Jiang H, Kelch S, Lendlein A. Polymers Move in Response to Light[J].Advanced Materials,2006,18（11）：1471-1475.
[59] Lendlein A, Jiang H, Jünger O, et al. Light-induced Shape-Memory Polymers[J].Nature,2005,434（7035）：879-882.
[60] Rosario R, Gust D, Hayes M, et al. Photon-Modulated Wettability Changes onSpiropyran-Coated Surfaces[J]. Langmuir,2002,18（21）：8062-8069.
[61] Kameda M, Sumaru K, Kanamori T, et al. Photoresponse Gas Permeability ofAzobenzene-Functionalized Glassy Polymer Films[J]. Journal of AppliedPolymer Science,2003,88（8）：2068-2072.
[62] Sumaru K, Ohi K, Takagi T, et al. Photoresponsive Properties of Poly(N-Isopropylacrylamide) Hydrogel Partly Modified with Spirobenzopyran[J].Langmuir,2006,22（9）：4353-4356.
[63] Garcia A, Marquez M, Cai T, et al. Photo-, Thermally, and pH-ResponsiveMicrogels[J]. Langmuir,2007,23（1）：224-229.
[64] Bisby R H, Mead C, Morgan C C. Wavelength programmed Solute ReleaseFrom Photosensitive Liposomes[J]. Biochemical and Biophysical ResearchCommunications,2000,276（1）：169-173.
[65] Mal N K, Fujiwara M, Tanaka Y, et al. Photo-Switched Storage and Release ofGuest Molecules in the Pore Void of Coumarin-Modified MCM-41[J].Chemistry of Materials,2003,15（17）：3385-3394.
[66] Szczubialka K, Nowakowska M. Response of Micelles Formed by SmartTerpolymers to Stimuli Studied by Dynamic Light Scattering[J]. Polymer,2003,44（18）：5269-5274.
[67] Eastoe J, Vesperinas A, Donnewirth A C, et al. Photodestructible Vesicles[J].Langmuir,2006,22（3）：851-853.
[68] Levrand B, Herrmann A. Light-Induced Controlled Release of FragranceAldehydes from1-Alkoxy-9,10-Anthraquinones for Applications in FunctionalPerfumery[C]. Flavour and Fragrance Journal,2006,21（3）：400-409.
[69] Zhao Y. Rational Design of Light-Controllable Polymer Micelles[J]. ChemicalRecord,2007,7（5）：286-294.
[70] Shum P, Kim J M, Thompson D H. Phototriggering of Liposomal Drug DeliverySystems[J]. Advanced Drug Delivery Reviews,2001,53（3）：273-284.
[71] Jiang J, Tong X, Morris D, et al. Toward Photocontrolled Release using Light-Dissociable Block Copolymer Micelles[J]. Macromolecules,2006,39（13）：4633-4640.
[72] Wang G, Tong X，Zhao Y. Preparation of Azobenzene-Containing AmphiphilicDiblock Copolymers for Light-Responsive Micellar Aggregates[J].Macromolecules,2004,37（24）：8911-8917.
[73] Tian F, Yu Y, Wang C, et al. Consecutive Morphological Transitions inNanoaggregates Assembled from Amphiphilic Random Copolymer Via Water-Driven Micellization and Light-Triggered Dissociation[J]. Macromolecules,2008,41（10）：3385-3388.
[74] Rijcken C J F, Soga O, Hennink W E，et al. Triggered Destabilisation ofPolymeric Micelles and Vesicles by Changing Polymers Polarity: an AttractiveTool for Drug Delivery[J]. Journal of Controlled Release,2007,120（3）：131-148.
[75] Lee C T, Smith K A, Hatton T A. Photoreversible Viscosity Changes andGelation in Mixtures of Hydrophobically Modified Polyelectrolytes andPhotosensitive Surfactants[J]. Macromolecules,2004,37（14）：5397-5405.
[76] Alvarez-Lorenzo C, Deshmukh S, Bromberg L, et al. Temperature-and Light-Responsive Blends of Pluronic F127and Poly (N, N-Dimethylacrylamide-Co-Methacryloyloxyazobenzene)[J]. Langmuir,2007,23（23）：11475-11481.
[77] Tong X, Wang G, Soldera A, et al. How Can Azobenzene Block CopolymerVesicles Be Dissociated and Reformed by Light[J]? The Journal of PhysicalChemistry B,2005,109（43）：20281-20287.
[78] Deshmukh S, Bromberg L, Smith K A, et al. Photoresponsive, AmphiphilicCopolymers of Azobenzene and N, N-Dimethylacrylamide[J]. PMSE Preprints,2006,95：878-880.
[79] Pouliquen G, Tribet C. Light-Triggered Association of Bovine Serum Albuminand Azobenzene-Modified Poly (Acrylic Acid) in Dilute and SemidiluteSolutions[J]. Macromolecules,2006,39（1）：373-383.
[80] Bonacucina G, Cespi M, Misici-Falzi M, et al. Colloidal Soft Matter as DrugDelivery System[J]. Journal of Pharmaceutical Sciences,2009,98（1）：1-42.
[81] Immordino M L, Dosio F, Cattel L. Stealth Liposomes: Review of the BasicScience, Rationale, and Clinical Applications, Existing and Potential[J].International Journal of Nanomedicine,2006,1（3）：297-315.
[82] Gerasimov O V, Boomer J A, Qualls M M, et al. Cytosolic Drug Delivery UsingpH-and Light-Sensitive Liposomes[J]. Advanced Drug Delivery Reviews,1999,38（3）：317-338.
[83] Yagai S, Karatsu T, Kitamura A. Photocontrollable Self-Assembly[J].Chemistry-A European Journal,2005,11（14）：4054-4063.
[84] Liu X M, Yang B, Wang Y L, et al. Photoisomerisable Cholesterol Derivatives asPhoto-Trigger of Liposomes: Effect of Lipid Polarity, Temperature,Incorporation Ratio, and Cholesterol[J]. Biochimica et Biophysica Acta,2005,1720（1-2）：28-34.
[85] Haraguchi K. Nanocomposite Hydrogels[J]. Current Opinion in Solid State&Materials Science,2007,11（3-4）：47-54.
[86] Sortino S. Nanostructured Molecular Films and Nanoparticles withPhotoactivable Functionalities[J]. Photochemical&Photobiological Sciences,2008,7（8）：911-924.
[87] Johansson E, Choi E, Angelos S, et al. Light-Activated FunctionalMesostructured Silica[C]. Journal of Sol-Gel Science and Technology,2008,46（3）：313-322.
[88] Slowing I I, Trewyn B G, Giri S, et al. Mesoporous Silica Nanoparticles forDrug Delivery and Biosensing Applications[J]. Advanced Functional Materials,2007,17（8）：1225-1236.
[89] Wu C, Chen C, Lai J, et al. Molecule-Scale Controlled-Release System Based onLight-Responsive Silica Nanoparticles[J]. Chemical Communications,2008,（23）：2662-2664.
[90] Weh K, Noack M, Hoffmann K, et al. Change of Gas Permeation byPhotoinduced Switching of Zeolite-Azobenzene Membranes of Type MFI andFAU[J]. Microporous and Mesoporous Materials,2002,54（1-2）：15-26.
[91] Angelos S, Choi E, Volgtle F, et al. Photo-Driven Expulsion of Molecules fromMesostructured Silica Nanoparticles[J]. Journal of Physical Chemistry C,2007,111（18）：6589-6592.
[92] Lu J, Choi E, Tamanoi F, et al. Light-Activated Nanoimpeller-Controlled DrugRelease in Cancer Cells[J]. Small,2008,4（4）：421-426.
[93] Dougherty T J, Gomer C J, Henderson B W, et al. Photodynamic Therapy[J].Journal of the National Cancer Institute,1998,90（12）：889-905.
[94] Dolmans D E, Fukumura D, Jain R K. Photodynamic Therapy for Cancer[J].Nature Reviews Cancer,2003,3（5）：380-387.
[95] Chen B, Roskams T, De Witte P A. Antivascular Tumor Eradication byHypericin-mediated Photodynamic Therapy[J]. Photochemistry andPhotobiology,2002,76（5）：509-513.
[96] Garg A D, Nowis D, Golab J, et al. Immunogenic Cell Death, Damps andAnticancer Therapeutics: An Emerging Amalgamation[J]. Biochimica etBiophysica Acta,2010,1805（1）：53-71.
[97] Ascencio M, Collinet P, Farine MO, et al. Protoporphyrin IX FluorescencePhotobleaching is a Useful Tool to Predict the Response of Rat Ovarian CancerFollowing Hexaminolevulinate Photodynamic Therapy[J]. Lasers in Surgery andMedicine,2008,40（5）：332-341.
[98] Sharman W M, Allen C M, Van Lier J E. Photodynamic Therapeutics: BasicPrinciples and Clinical Applications[J]. Drug Discovery Today,1999,4（11）：507-517.
[99] De Rosa F S, Bentley M V. Photodynamic Therapy of Skin Cancers: Sensitizers,Clinical Studies and Future Directives[J]. Pharmaceutical Research,2000,17（12）：1447-1455.
[100] Hamblin M R, Newman E L. On the Mechanism of the Tumour-LocalisingEffect in Photodynamic Therapy[J]. Journal of Photochemistry andPhotobiology B,1994,23（1）：3-8.
[101] Iyer A K, Greish K, Seki T, et al. Polymeric Micelles of Zinc Protoporphyrinfor Tumor Targeted Delivery Based on EPR Effect and Singlet OxygenGeneration[J]. Journal of Drug Targeting,2007,15（7-8）：496-506.
[102] Kessel D. The Role of Low-Density Lipoprotein in the Biodistribution ofPhotosensitizing Agents[J]. Journal of Photochemistry and Photobiology B,1992,14（3）：261-266.
[103] Sibani S A, Mccarron P A, Woolfson A D, et al. Photosensitiser Delivery forPhotodynamic Therapy. Part2: Systemic Carrier Platforms[J]. Expert Opinionon Drug Delivery,2008,5（11）：1241-1254.
[104] Foote C S. Mechanisms of Photosensitized Oxidation. There are SeveralDifferent Types of Photosensitized Oxidation Which May be Important inBiological Systems[J]. Science,1968,162：963-970.
[105] Dysart J S, Patterson M S. Characterization of Photofrin Photobleaching forSinglet Oxygen Dose Estimation During Photodynamic Therapy of MLL Cellsin Vitro[J]. Physics in Medicine and Biology,2005,50（11）：2597-2616.
[106] Moan J, Berg K, Kvam E, et al. Intracellular Localization ofPhotosensitizers[J]. Ciba Foundation Symposium,1989,146：95-111.
[107] Allison R R, Sibata C H. Oncologic Photodynamic Therapy Photosensitizers: aClinical Review[J]. Photodiagnosis Photodynamic Therapy,2010,7（2）：61-75.
[108] Buytaert E, Dewaele M, Agostinis P. Molecular Effectors of Multiple CellDeath Pathways Initiated by Photodynamic Therapy[J]. Biochimica etBiophysica Acta,2007,1776（1）：86-107.
[109] Kessel D, Castelli M. Evidence That Bcl-2is the Target of ThreePhotosensitizers that Induce a Rapid Apoptotic Response[J]. Photochemistryand Photobiology,2001,74（2）：318-322.
[110] Kessel D. Relocalization of Cationic Porphyrins During PhotodynamicTherapy[J]. Photochemical&Photobiological Sciences,2002,1（11）：837-840.
[111] Vanlangenakker N, Vanden Berghe T, Krysko D V, et al. MolecularMechanisms and Pathophysiology of Necrotic Cell Death[J]. CurrentMolecular Medicine,2008,8（3）：207-220.
[112] Reiners J J Jr, Agostinis P, Berg K, et al. Assessing Autophagy in the Contextof Photodynamic Therapy[J]. Autophagy,2010,6（1）：7-18.
[113] Dewaele M, Maes H, Agostinis P. ROS-Mediated Mechanisms of AutophagyStimulation and their Relevance in Cancer Therapy[J]. Autophagy,2010,6（7）：838-854.
[114] Celli J P, Spring B Q, Rizvi I, et al. Imaging and Photodynamic Therapy:Mechanisms, Monitoring, and Optimization[J]. Chemical Reviews,2010,110（5）：2795-2838.
[115] Alvarez-Lorenzo C, Bromberg L, Concheiro A. Light-Sensitive IntelligentDrug Delivery Systems[J]. Photochemistry and Photobiology,2009,85（4）：848-860.
[116] Young S W, Qing F, Harriman A, et al. Gadolinium (III) Texaphyrin: a TumorSelective Radiation Sensitizer that is Detectable by MRI[J]. Proceedings of theNational Academy of Sciences,1996,93（13）：6610-6615.
[117] Hofmann B, Bogdanov A, Marecos E, et al. Mechanism of Gadophrin-2Accumulation in Tumor Necrosis. Journal of Magnetic Resonance Imaging[J].1999,9（2）：336-341.
[118] Li G L, Slansky A, Dobhal M P, et al. Chlorophyll-a Analogues Conjugatedwith Aminobenzyl-DTPA as Potential Bifunctional Agents for MagneticResonance Imaging and Photodynamic Therapy[J]. Bioconjugate Chemistry,2005,16（1）：32-42.
[119] Spernyak J A, White W H, Ethirajan M, et al. Hexylether Derivative ofPyropheophorbide-A (HPPH) on Conjugating With3gadolinium(III)Aminobenzyldiethylenetriaminepentaacetic Acid Shows Potential for in VivoTumor Imaging (MR, Fluorescence) and Photodynamic Therapy[J].Bioconjugate Chemistry,2010,21（5）：828-835.
[120] Mosmann T. Rapid Colorimetric Assay for Cellular Growth and Survival:Application to Proliferation and Cytotoxicity Assays[J]. Journal ofImmunological Methods,1983,65：55-63.
[121] He Q, Shi J. Mesoporous Silica Nanoparticle Based Nano Drug DeliverySystems: Synthesis, Controlled Drug Release and Delivery, Pharmacokineticsand Biocompatibility[J]. Journal of Materials Chemistry,2011,21（16）：5845-5855.
[122] Vivero-Escoto J L, Slowing I I, Trewyn B G, et al. Mesoporous SilicaNanoparticles for Intracellular Controlled Drug Delivery[J]. Small,2010,6（18）：1952-1967.
[123] Wang X, Yang L, Chen Z G, et al. Application of Nanotechnology in CancerTherapy and Imaging[J]. A Cancer Journal for Clinicians,2008,58（2）：97-110.
[124] Zamboni W C. Liposomal, Nanoparticle, and Conjugated Formulations ofAnticancer Agents[J]. Clinical Cancer Research,2005,11（23）：8230-8234.
[125] Li S D, Chen Y C, Hackett M J, et al. Tumor-targeted Delivery of SiRNA bySelf-assembled Nanoparticles[J]. Molecular Therapy,2008,16（1）：163-169.
[126] Anderson P M, Hanson D C, Hasz D E, et al. Cytokines in Liposomes:Preliminary Studies with IL-1, IL-2, IL-6, GM-CSF and Interferongamma[J].Cytokines,1994,6（1）：92-101.
[127] Ye Q, Asherman J, Stevenson M, et al. DepoFoam Technology: a Vehicle forControlled Delivery of Protein and Peptide Drugs[C]. Journal of ControlledRelease,2000,64（1-3）：155-166.
[128] Cullis P R, Hope M J, Bally M B, et al. Influence of pH Gradients on the TransBilayer Transport of Drugs, Lipids, Peptides and Metal Ions into LargeUnilamellar Vesicles[J]. Biochimica et Biophysica Acta,1997,1331（2）：187-211.
[129] Huang C H. Phosphatidylcholine Vesicles. Formation and PhysicalCharacteristics[J]. Biochemistry,1969,8：344-352.
[130] Anzai J-I, Osa T. Photosensitive Artificial Membranes Based on Azobenzeneand Spirobenzopyran Derivatives[J]. Tetrahedron,1994,50（14）：4039-4070.
[131] Ma Y, Dai Z, Gao Y, et al. Liposomal Architecture Boosts Biocompatibility ofNanohybrid Cerasomes. Nanotoxicology[J].2011,5（4）：622-635.
[132] Wu Y, Demachi Y, Tsutsumi O, et al. Photoinduced Alignment of PolymerLiquid Crystals Containing Azobenzene Moieties in the Side Chain.3. Effectof Structure of Photochromic Moieties on Alignment Behavior[J].Macromolecules,1998,31（14）：4457-4463.
[133] Park C, Lim J, Yun M, et al. Photoinduced Release of Guest Molecules bySupramolecular Transformation of Self-assembled Aggregates Derived fromDendrons[J]. Angewandte Chemie International Edition,2008,47（16）：2959-2963.
[134] Gillies E R, Jonsson T B, Fréchet J M J. Stimuli-Responsive SupramolecularAssemblies of Linear-Dendritic Copolymers[J]. Journal of the AmericanChemical Society,2004,126（38）：11936-11943.
[135] Angelos S, Yang Y-W, Khashab N M, et al. Dual-Controlled NanoparticlesExhibiting AND Logic[J]. Journal of the American Chemical Society,2009,131（32）：11344-11346.
[136] Chen B, Pogue B W, Hasan T. Liposomal Delivery of PhotosensitisingAgents[J]. Expert Opinion on Drug Delivery,2005,2（3）：477-487.
[137] Roy I, Ohulchanskyy T Y, Pudavar H E, et al. Ceramic-Based NanoparticlesEntrapping Water-Insoluble Photosensitizing Anticancer Drugs: A Novel Drug-Carrier System For Photodynamic Therapy[J]. Journal of the AmericanChemical Society,2003,125（26）：7860-7865.
[138] Ohulchanskyy T Y, Roy I, Goswami L N, et al. Organically Modified SilicaNanoparticles with Covalently Incorporated Photosensitizer for PhotodynamicTherapy of Cancer[J]. Nano Letters,2007,7（9）：2835-2842.
[139] van Nostrum C F. Polymeric Micelles to Deliver Photosensitizers forPhotodynamic Therapy[J]. Advanced Drug Delivery Reviews,2004,56（1）：9-16.
[140] Wang S, Gao R, Zhou F, et al. Nanomaterials and Singlet OxygenPhotosensitizers: Potential Applications in Photodynamic Therapy[J]. Journalof Materials Chemistry,2004,14（4）：487-493.
[141] Gao D, Agayan R R, Xu H, et al. Nanoparticles for Two-photon PhotodynamicTherapy in Living Cells[J]. Nano Letters,2006,6（11）：2383-2386.
[142] Derycke A S L, deWitte P A M. Liposomes for Photodynamic Therapy[J].Advanced Drug Delivery Reviews,2004,56（1）：17-30.
[143] Lovell J F, Jin C S, Huynh E, et al. Porphysome Nanovesicles Generated byPorphyrin Bilayers for Use as Multimodal Biophotonic Contrast Agents[J].Nature Materials,2011,10（4）：324-332.
[144] Lindig B A, Rodgers M A J, Schaap A P. Determination of the Lifetime ofSinglet Oxygen in D2O Using9,10-Anthracenedipropionic Acid, a Water-Soluble Probe[J]. Journal of the American Chemical Society,1980,102（17）：5590-5593.
[145] Dzwigaj S, Pezerat H. Singlet Oxygen-trapping Reaction as a Method of1O2detection: role of some reducing agents[J]. Free Radical Research,1995,23（2）：103-115.
[146] Guelluy P-H, Fontaine-Aupart M-P, Grammenos A, et al. OptimizingPhotodynamic Therapy by Liposomal Formulation of the PhotosensitizerPyropheophorbide-a Methyl Ester: in Vitro and ex Vivo ComparativeBiophysical Investigations in a Colon Carcinoma Cell Line[J]. Photochemistryand Photobiology,2010,9（9）：1252-1260.
[147] Huang X L, Teng X, Chen D, et al. The Effect of the Shape of MesoporousSilica Nanoparticles on Cellular Uptake and Cell Function[J]. Biomaterials,2010,31（3）：438-448.
[148] Ideta R, Tasaka F, Jang W-D, et al. Nanotechnology-Based PhotodynamicTherapy for Neovascular Disease using a Supramolecular Nanocarrier loadedwith a Dendritic Photosensitizer[J]. Nano Letters,2005,5（12）：2426-2431.
[149] Pan D, Caruthers S D, Senpan A, et al. Revisiting an Old Friend: Manganese-based MRI Contrast Agents[J]. WIREs Nanomedicine and Nanobiotechnology,2011,3（2）：162-173.
[150] Zhang X A, Lovejoy K S, Jasanoff A, et al. Water-soluble Porphyrins as aDual-Function Molecular Imaging Platform for MRI and Fluorescence ZincSensing[J]. Proceedings of the National Academy of Sciences,2007,104（26）：10780-10785.
[151] Chen C W, Cohen J S, Myers C E, et al. Paramagnetic Metalloporphyrins asPotential Contrast Agents in NMR Imaging[J]. FEBS Letters,1984,168:70-74.
[152] Koenig S H, Brown R D,3rd, et al. The Anomalous Relaxivity of Mn3+(TPPS4)[J]. Magnetic Resonance in Medicine,1987,4（3）：252-260.
[153] Fiel R J, Button T M, Gilani S, et al. Proton Relaxation Enhancement byManganese (III) TPPS4in a Model Tumor System[J]. Magnetic ResonanceImaging,1987,5（2）：149-156.
[154] Lyon R C, Faustino P J, Cohen J S, et al. Tissue Distribution and Stability ofMetalloporphyrin MRI Contrast Agents[J]. Magnetic Resonance in Medicine,1987,4（1）：24-33.
[155] Woodburn K W. Intracellular Localization of the Radiation EnhancerMotexafin Gadolinium using Interferometric Fourier FluorescenceMicroscopy[J]. Journal of Pharmacology and Experimental Therapeutics,2001,297（3）：888-894.
[156] Zhang Z, He R, Yan K, et al. Synthesis and In Vitro and In Vivo Evaluation ofManganese (III) Porphyrin–Dextran as a Novel MRI Contrast Agent[J].Bioorganic&Medicinal Chemistry Letters,2009,19（23）：6675-6678.
[2] Charman W N, Chan H-K, Finnin B C，et al. Drug Delivery: A Key Factor inRealising the Full Therapeutic Potential of Drugs[J]. Drug DevelopmentResearch,1999,46（3-4）：316-327.
[3] Kopecek J. Smart and Genetically Engineered Biomaterials and Drug DeliverySystems[J]. European Journal of Pharmaceutical Sciences,2003,20（1）：1-16.
[4] Torchilin V P. Structure and Design of Polymeric Surfactant-Based DrugDelivery Systems[J]. Journal of Controlled Release,2001,73（2-3）：137-172.
[5] Bergh J. Quo Vadis with Targeted Drugs in the21st Century[J]? Journal ofClinical Oncology,2009,27（1）：2-5.
[6] Fojo T, Grady C. How Much is Life Worth: Cetuximab, Non-Small Cell LungCancer, and the$440Billion Question[J]. Journal of the National CancerInstitute,2009,101（15）：1044-1048.
[7] Hampton T. Targeted Cancer Therapies Lagging: Better Trial Design CouldBoost Success Rate[J]. Journal of the American Medical Association,2006,296（16）：1951-1952.
[8] Rai A J, Yee J, Fleisher M. Biomarkers in the Era of Personalized Medicine-aMultiplexed SNP Assay Using Capillary Electrophoresis for Assessing DrugMetabolism Capacity[J]. Scandinavian Journal of Clinical and LaboratoryInvestigation,2010,70（242）：15-18.
[9] Blanchet K D. Redefining Personalized Medicine in the Postgenomic Era:Developing Bladder Cancer Therapeutics with Proteomics[J]. British Journal ofUrology International,2010,105（2）：i-iii.
[10] Francke U. On the Bumpy Road Towards ‘Personalized Medicine’[J]. EMBOMolecular Medicine,2010,2（1）：1-2.
[11] Bates S. Progress Towards Personalized Medicine[J]. Drug Discovery Today,2010,15（3-4）：115-120.
[12] Espina V, Liotta L A, Petricoin III E F. Reverse-Phase Protein Microarrays forTheranostics and Patient Tailored Therapy[J]. Methods in Molecular Biology,2009,520：89-105.
[13] Falk J. Epigenetics&Sequencing-Gene Expression Systems' SecondInternational Meeting. Chromatin Methylation to Disease Biology&Theranostics[J]. Idrugs,2008,11（9）：650-652.
[14] Muller-Goymann C C. Physicochemical Characterization of Colloidal DrugDelivery Systems such as Reverse Micelles, Vesicles, Liquid Crystals AndNanoparticles for Topical Administration[J]. European Journal ofPharmaceutics and Biopharmaceutics,2004,58（2）：343-356.
[15] Haag R. Supramolecular Drug-Delivery Systems Based on Polymeric Core-Shell Architectures[J]. Angewandte Chemie International Edition,2004,43（3）：278-282.
[16] Gaucher G, Dufresne M-H, Sant V P, et al. Block Copolymer Micelles:Preparation, Characterization and Application in Drug Delivery[J]. Journal ofControlled Release,2005,109（1-3）：169-188.
[17] Nallamothu R, Wood G C, Pattillo C B, et al. A Tumor Vasculature TargetedLiposome Delivery System for Combretastatin A4: Design, Characterization,and in Vitro Evaluation[J]. AAPS Pharmscitech,2006,7（2）：E1-E10.
[18] Pal K, Banthia A K, Majumdar D K. Polymeric Hydrogels: Characterization andBiomedical Applications[J]. Designed Monomers and Polymers,2009,12（3）：197-220.
[19] Huo Q, Margolese D I, Stucky G D. Surfactant Control of Phases in theSynthesis of Mesoporous Silica-Based Materials[J]. Chemistry of Materials,1996,8（5）：1147-1160.
[20] Shimojima A, Sugahara Y, Kuroda K. Inorganic-Organic Layered MaterialsDerived Via the Hydrolysis and Polycondensation of Trialkoxy(Alkyl)Silanes[J].Bulletin of the Chemical Society of Japan,1997,70（11）：2847-2853.
[21] Moreau J J E, Vellutini L, Man M W C, et al. Self-Organized Hybrid Silica withLong-Range Ordered Lamellar Structure[J]. Journal of the American ChemicalSociety,2001,123（32）：7957-7958.
[22] Ruiz-Hitzky E, Letaief S, Prévot V. Novel Organic-Inorganic Mesophases: Self-templating Synthesis and Intratubular Swelling[J]. Advanced Materials,2002,14（6）：439-443.
[23] Zhang Q, Ariga K, Okabe A, et al. A Condensable Amphiphile with a CleavableTail as a “Lizard” Template for the Sol Gel Synthesis of FunctionalizedMesoporous Silica[J]. Journal of the American Chemical Society,2004,126（4）：988-989.
[24] Katagiri K, Ariga K, Kikuchi J. Preparation of Organic-Inorganic Hybrid Vesicle"Cerasome" Derived from Artificial Lipid with Alkoxysilyl Head[J]. ChemistryLetters,1999,（7）：661-662.
[25] Kunitake T. Synthetic Bilayer Membranes: Molecular Design, Self-Organization,and Application[J]. Angewandte Chemie International Edition,1992,31（6）：709-726.
[26] Israelachivili J N, Mitchell D J, Ninham B W. Theory of Self-Assembly ofHydrocarbon Amphiphiles into Micelles and Bilayers[J]. Journal of theChemical Society, Faraday Transactions,1976,72：1525-1568.
[27] Hashizume M, Kawanami S, Iwamoto S, et al. Stable Vesicular Nanoparticle“Cerasome” as an Organic-Inorganic Hybrid Formed with OrganoalkoxysilaneLipids Having a Hydrogen-Bonding Unit[C]. Thin Solid Films,2003,438-439：20-26.
[28] Katagiri K, Hamasaki R, Ariga K, et al. Layered Paving of VesicularNanoparticles Formed with Cerasome as a Bioinspired Organic-InorganicHybrid[J]. Journal of the American Chemical Society,2002,124（27）：7892-7893.
[29] Sasaki Y, Matsui K, Aoyama Y, et al. Cerasome as an infusible and Cell friendlyGene Carrier: Synthesis of Cerasome-forming Lipids and Transfection usingCerasome[J]. Nature Protocols,2006,1（3）：1227-1234.
[30] Hashizume M, Inoue H, Katagiri K, et al. Cerasome as an Organic-Inorganicvesicular Nanohybrid. Characterization of Cerasome-forming Lipids Having aSingle or a Dual Trialkoxysilyl Head[C]. Journal of Sol-Gel Science andTechnology,2004,31（1-3）：99-102.
[31] Katagiri K, Hashizume M, Ariga K, et al. Preparation and Characterization of aNovel Organic-Inorganic Nanohybrid "Cerasome" formed with a LiposomalMembrane and Silicate Surface[J]. Chemistry-A European Journal,2007,13（18）：5272-5281.
[32] Ariga K, Katagiri K, Kikuchi J. Preparation Condition of a Novel Organic-Inorganic Hybrid Vesicle “Cerasome”[J]. Kobunshi Ronbunshu,2000,57（4）：251-253.
[33] Katagiri K, Ariga K, Kikuchi J. Novel Class of Organic-Inorganic HybridVesicle “Cerasome” Derived from various Amphiphiles with AlkoxysilylHead[J]. Studies in Surface Science and Catalysis,2001,132：599-602.
[34] Katagiri K, Hamasaki R, Ariga K, et al. Preparation and Surface Modification ofNovel Vesicular Nano-Particle “Cerasome” with Liposomal Bilayer and SilicateSurface[C]. Journal of Sol-Gel Science and Technology,2003,26（1-3）：393-396.
[35] Cao Z, Ma Y, Yue X, et al. Stabilized Liposomal Nanohybrid Cerasomes forDrug Delivery Applications[J]. Chemical Communications,2010,46（29）：5265-5267.
[36] Sasaki Y, Yamada M, Terashima T, et al. Construction of IntermolecularCommunication System on “Cerasome” as an Organic-Inorganic Nanohybrid[J].Kobunshi Ronbunshu,2004,61（10）：541-546.
[37] Katagiri K, Hamasaki R, Ariga K, et al. Layer-by-layer Self-Assembling ofLiposomal Nanohybrid “Cerasome” on Substrates[J]. Langmuir,2002,18（17）：6709-6711.
[38] Katagiri K, Hamasaki R, Hashizume M, et al. Size-Selective Organization ofSilica and Silica-Like Particles on Solid Interfaces through Layer-by-layerAssembly[C]. Journal of Sol-Gel Science and Technology,2004,31（1-3）：59-62.
[39] Matsui K, Sasaki Y, Komatsu T, et al. RNAi Gene Silencing Using Cerasome asa Viral-Size siRNA-Carrier free from Fusion and Crosslinking[J]. Bioorganic&Medicinal Chemistry Letters,2007,17（14）：3935-3938.
[40] Hashizume M, Sasaki Y, Terashima T, et al. Creation of Organized Assembly ofCerasomes on DNA Templates[J]. Kobunshi Ronbunshu,2008,65（6）：421-426.
[41] Kabanov A V, Kabanov V A. DNA Complexes with Polycations for the Deliveryof Genetic Material into Cells[J]. Bioconjugate Chemistry,1995,6（1）：7-20.
[42] Mintzer M A, Simanek E E. Nonviral Vectors for Gene Delivery[J]. ChemicalReviews,2009,109（2）：259-302.
[43] Matsui K, Sando S, Sera T, et al. Cerasome as an Infusible, Cell-Friendly, andSerum-Compatible Transfection Agent in a Viral Size[J]. Journal of theAmerican Chemical Society,2006,128（10）：3114-3115.
[44] Vauthier C, Labarre D. Modular Biomimetic Drug. Delivery Systems[J]. Journalof Drug Delivery Science&Technology,2008,18（1）：59-68.
[45] Bayer C L, Peppas N A. Advances in Recognitive, Conductive and ResponsiveDelivery Systems[J]. Journal of Controlled Release,2008,132（3）：216-221.
[46] Youan B B C. Chronopharmaceutics: Gimmick or Clinically Relevant Approachto Drug Delivery[J]? Journal of Controlled Release,2004,98（3）：337-353.
[47] Alvarez-Lorenzo C, Concheiro A. Intelligent Drug Delivery Systems: PolymericMicelles and Hydrogels[J]. Mini-Reviews in Medicinal Chemistry,2008,8（11）：1065-1074.
[48] Anil A K. Stimuli-Induced Pulsatile or Triggered Release Delivery Systems forBioactive Compounds. Recent Pat. Endocr., Metab[P]. Immune Drug Discovery,2007,1：83-90.
[49] Kost J, Langer R. Responsive Polymeric Delivery Systems[J]. Advanced DrugDelivery Reviews,2001,46（1-3）：125-148.
[50] Sershen S, Wes J. Implantable, Polymeric Systems for Modulated DrugDelivery[J]. Advanced Drug Delivery Reviews,2002,54（9）：1225-1235.
[51] Qiu Y, Park K. Environment-Sensitive Hydrogels for Drug Delivery[J].Advanced Drug Delivery Reviews,2001,53（3）：321-339.
[52] Murdan S. Electro-Responsive Drug Delivery from Hydrogels[J]. Journal ofControlled Release,2003,92（1-2）：1-17.
[53] Sunil A, Kulkarni R V, Mallikarjuna N N, et al. Electrically ModulatedTransport of Diclofenac Salts Through Hydrogels of Sodium Alginate, Carbopol,and Their Blend Polymers[C]. Journal of Applied Polymer Science,2005,96（2）：301-311.
[54] Rapoport N. Physical Stimuli-Responsive Polymeric Micelles for Anti-CancerDrug Delivery[J]. Progress in Polymer Science,2007,32（8-9）：962-990.
[55] Andresen T L, Jensen S S, Jorgensen K. Advanced Strategies in LiposomalCancer Therapy: Problems and Prospects of Active and Tumor Specific DrugRelease[J]. Progress in Lipid Research,2005,44（1）：68-97.
[56] Chung C M, Roh Y S, Cho S Y, et al. Crack Healing in Polymeric Materials ViaPhotochemical [2+2] Cycloaddition[J]. Chemistry of Materials,2004,16（21）：3982-3984.
[57] Wu D Y, Meure S, Solomon D. Self-Healing Polymeric Materials: a Review ofRecent Developments[J]. Progress in Polymer Science,2008,33（5）：479-522.
[58] Jiang H, Kelch S, Lendlein A. Polymers Move in Response to Light[J].Advanced Materials,2006,18（11）：1471-1475.
[59] Lendlein A, Jiang H, Jünger O, et al. Light-induced Shape-Memory Polymers[J].Nature,2005,434（7035）：879-882.
[60] Rosario R, Gust D, Hayes M, et al. Photon-Modulated Wettability Changes onSpiropyran-Coated Surfaces[J]. Langmuir,2002,18（21）：8062-8069.
[61] Kameda M, Sumaru K, Kanamori T, et al. Photoresponse Gas Permeability ofAzobenzene-Functionalized Glassy Polymer Films[J]. Journal of AppliedPolymer Science,2003,88（8）：2068-2072.
[62] Sumaru K, Ohi K, Takagi T, et al. Photoresponsive Properties of Poly(N-Isopropylacrylamide) Hydrogel Partly Modified with Spirobenzopyran[J].Langmuir,2006,22（9）：4353-4356.
[63] Garcia A, Marquez M, Cai T, et al. Photo-, Thermally, and pH-ResponsiveMicrogels[J]. Langmuir,2007,23（1）：224-229.
[64] Bisby R H, Mead C, Morgan C C. Wavelength programmed Solute ReleaseFrom Photosensitive Liposomes[J]. Biochemical and Biophysical ResearchCommunications,2000,276（1）：169-173.
[65] Mal N K, Fujiwara M, Tanaka Y, et al. Photo-Switched Storage and Release ofGuest Molecules in the Pore Void of Coumarin-Modified MCM-41[J].Chemistry of Materials,2003,15（17）：3385-3394.
[66] Szczubialka K, Nowakowska M. Response of Micelles Formed by SmartTerpolymers to Stimuli Studied by Dynamic Light Scattering[J]. Polymer,2003,44（18）：5269-5274.
[67] Eastoe J, Vesperinas A, Donnewirth A C, et al. Photodestructible Vesicles[J].Langmuir,2006,22（3）：851-853.
[68] Levrand B, Herrmann A. Light-Induced Controlled Release of FragranceAldehydes from1-Alkoxy-9,10-Anthraquinones for Applications in FunctionalPerfumery[C]. Flavour and Fragrance Journal,2006,21（3）：400-409.
[69] Zhao Y. Rational Design of Light-Controllable Polymer Micelles[J]. ChemicalRecord,2007,7（5）：286-294.
[70] Shum P, Kim J M, Thompson D H. Phototriggering of Liposomal Drug DeliverySystems[J]. Advanced Drug Delivery Reviews,2001,53（3）：273-284.
[71] Jiang J, Tong X, Morris D, et al. Toward Photocontrolled Release using Light-Dissociable Block Copolymer Micelles[J]. Macromolecules,2006,39（13）：4633-4640.
[72] Wang G, Tong X，Zhao Y. Preparation of Azobenzene-Containing AmphiphilicDiblock Copolymers for Light-Responsive Micellar Aggregates[J].Macromolecules,2004,37（24）：8911-8917.
[73] Tian F, Yu Y, Wang C, et al. Consecutive Morphological Transitions inNanoaggregates Assembled from Amphiphilic Random Copolymer Via Water-Driven Micellization and Light-Triggered Dissociation[J]. Macromolecules,2008,41（10）：3385-3388.
[74] Rijcken C J F, Soga O, Hennink W E，et al. Triggered Destabilisation ofPolymeric Micelles and Vesicles by Changing Polymers Polarity: an AttractiveTool for Drug Delivery[J]. Journal of Controlled Release,2007,120（3）：131-148.
[75] Lee C T, Smith K A, Hatton T A. Photoreversible Viscosity Changes andGelation in Mixtures of Hydrophobically Modified Polyelectrolytes andPhotosensitive Surfactants[J]. Macromolecules,2004,37（14）：5397-5405.
[76] Alvarez-Lorenzo C, Deshmukh S, Bromberg L, et al. Temperature-and Light-Responsive Blends of Pluronic F127and Poly (N, N-Dimethylacrylamide-Co-Methacryloyloxyazobenzene)[J]. Langmuir,2007,23（23）：11475-11481.
[77] Tong X, Wang G, Soldera A, et al. How Can Azobenzene Block CopolymerVesicles Be Dissociated and Reformed by Light[J]? The Journal of PhysicalChemistry B,2005,109（43）：20281-20287.
[78] Deshmukh S, Bromberg L, Smith K A, et al. Photoresponsive, AmphiphilicCopolymers of Azobenzene and N, N-Dimethylacrylamide[J]. PMSE Preprints,2006,95：878-880.
[79] Pouliquen G, Tribet C. Light-Triggered Association of Bovine Serum Albuminand Azobenzene-Modified Poly (Acrylic Acid) in Dilute and SemidiluteSolutions[J]. Macromolecules,2006,39（1）：373-383.
[80] Bonacucina G, Cespi M, Misici-Falzi M, et al. Colloidal Soft Matter as DrugDelivery System[J]. Journal of Pharmaceutical Sciences,2009,98（1）：1-42.
[81] Immordino M L, Dosio F, Cattel L. Stealth Liposomes: Review of the BasicScience, Rationale, and Clinical Applications, Existing and Potential[J].International Journal of Nanomedicine,2006,1（3）：297-315.
[82] Gerasimov O V, Boomer J A, Qualls M M, et al. Cytosolic Drug Delivery UsingpH-and Light-Sensitive Liposomes[J]. Advanced Drug Delivery Reviews,1999,38（3）：317-338.
[83] Yagai S, Karatsu T, Kitamura A. Photocontrollable Self-Assembly[J].Chemistry-A European Journal,2005,11（14）：4054-4063.
[84] Liu X M, Yang B, Wang Y L, et al. Photoisomerisable Cholesterol Derivatives asPhoto-Trigger of Liposomes: Effect of Lipid Polarity, Temperature,Incorporation Ratio, and Cholesterol[J]. Biochimica et Biophysica Acta,2005,1720（1-2）：28-34.
[85] Haraguchi K. Nanocomposite Hydrogels[J]. Current Opinion in Solid State&Materials Science,2007,11（3-4）：47-54.
[86] Sortino S. Nanostructured Molecular Films and Nanoparticles withPhotoactivable Functionalities[J]. Photochemical&Photobiological Sciences,2008,7（8）：911-924.
[87] Johansson E, Choi E, Angelos S, et al. Light-Activated FunctionalMesostructured Silica[C]. Journal of Sol-Gel Science and Technology,2008,46（3）：313-322.
[88] Slowing I I, Trewyn B G, Giri S, et al. Mesoporous Silica Nanoparticles forDrug Delivery and Biosensing Applications[J]. Advanced Functional Materials,2007,17（8）：1225-1236.
[89] Wu C, Chen C, Lai J, et al. Molecule-Scale Controlled-Release System Based onLight-Responsive Silica Nanoparticles[J]. Chemical Communications,2008,（23）：2662-2664.
[90] Weh K, Noack M, Hoffmann K, et al. Change of Gas Permeation byPhotoinduced Switching of Zeolite-Azobenzene Membranes of Type MFI andFAU[J]. Microporous and Mesoporous Materials,2002,54（1-2）：15-26.
[91] Angelos S, Choi E, Volgtle F, et al. Photo-Driven Expulsion of Molecules fromMesostructured Silica Nanoparticles[J]. Journal of Physical Chemistry C,2007,111（18）：6589-6592.
[92] Lu J, Choi E, Tamanoi F, et al. Light-Activated Nanoimpeller-Controlled DrugRelease in Cancer Cells[J]. Small,2008,4（4）：421-426.
[93] Dougherty T J, Gomer C J, Henderson B W, et al. Photodynamic Therapy[J].Journal of the National Cancer Institute,1998,90（12）：889-905.
[94] Dolmans D E, Fukumura D, Jain R K. Photodynamic Therapy for Cancer[J].Nature Reviews Cancer,2003,3（5）：380-387.
[95] Chen B, Roskams T, De Witte P A. Antivascular Tumor Eradication byHypericin-mediated Photodynamic Therapy[J]. Photochemistry andPhotobiology,2002,76（5）：509-513.
[96] Garg A D, Nowis D, Golab J, et al. Immunogenic Cell Death, Damps andAnticancer Therapeutics: An Emerging Amalgamation[J]. Biochimica etBiophysica Acta,2010,1805（1）：53-71.
[97] Ascencio M, Collinet P, Farine MO, et al. Protoporphyrin IX FluorescencePhotobleaching is a Useful Tool to Predict the Response of Rat Ovarian CancerFollowing Hexaminolevulinate Photodynamic Therapy[J]. Lasers in Surgery andMedicine,2008,40（5）：332-341.
[98] Sharman W M, Allen C M, Van Lier J E. Photodynamic Therapeutics: BasicPrinciples and Clinical Applications[J]. Drug Discovery Today,1999,4（11）：507-517.
[99] De Rosa F S, Bentley M V. Photodynamic Therapy of Skin Cancers: Sensitizers,Clinical Studies and Future Directives[J]. Pharmaceutical Research,2000,17（12）：1447-1455.
[100] Hamblin M R, Newman E L. On the Mechanism of the Tumour-LocalisingEffect in Photodynamic Therapy[J]. Journal of Photochemistry andPhotobiology B,1994,23（1）：3-8.
[101] Iyer A K, Greish K, Seki T, et al. Polymeric Micelles of Zinc Protoporphyrinfor Tumor Targeted Delivery Based on EPR Effect and Singlet OxygenGeneration[J]. Journal of Drug Targeting,2007,15（7-8）：496-506.
[102] Kessel D. The Role of Low-Density Lipoprotein in the Biodistribution ofPhotosensitizing Agents[J]. Journal of Photochemistry and Photobiology B,1992,14（3）：261-266.
[103] Sibani S A, Mccarron P A, Woolfson A D, et al. Photosensitiser Delivery forPhotodynamic Therapy. Part2: Systemic Carrier Platforms[J]. Expert Opinionon Drug Delivery,2008,5（11）：1241-1254.
[104] Foote C S. Mechanisms of Photosensitized Oxidation. There are SeveralDifferent Types of Photosensitized Oxidation Which May be Important inBiological Systems[J]. Science,1968,162：963-970.
[105] Dysart J S, Patterson M S. Characterization of Photofrin Photobleaching forSinglet Oxygen Dose Estimation During Photodynamic Therapy of MLL Cellsin Vitro[J]. Physics in Medicine and Biology,2005,50（11）：2597-2616.
[106] Moan J, Berg K, Kvam E, et al. Intracellular Localization ofPhotosensitizers[J]. Ciba Foundation Symposium,1989,146：95-111.
[107] Allison R R, Sibata C H. Oncologic Photodynamic Therapy Photosensitizers: aClinical Review[J]. Photodiagnosis Photodynamic Therapy,2010,7（2）：61-75.
[108] Buytaert E, Dewaele M, Agostinis P. Molecular Effectors of Multiple CellDeath Pathways Initiated by Photodynamic Therapy[J]. Biochimica etBiophysica Acta,2007,1776（1）：86-107.
[109] Kessel D, Castelli M. Evidence That Bcl-2is the Target of ThreePhotosensitizers that Induce a Rapid Apoptotic Response[J]. Photochemistryand Photobiology,2001,74（2）：318-322.
[110] Kessel D. Relocalization of Cationic Porphyrins During PhotodynamicTherapy[J]. Photochemical&Photobiological Sciences,2002,1（11）：837-840.
[111] Vanlangenakker N, Vanden Berghe T, Krysko D V, et al. MolecularMechanisms and Pathophysiology of Necrotic Cell Death[J]. CurrentMolecular Medicine,2008,8（3）：207-220.
[112] Reiners J J Jr, Agostinis P, Berg K, et al. Assessing Autophagy in the Contextof Photodynamic Therapy[J]. Autophagy,2010,6（1）：7-18.
[113] Dewaele M, Maes H, Agostinis P. ROS-Mediated Mechanisms of AutophagyStimulation and their Relevance in Cancer Therapy[J]. Autophagy,2010,6（7）：838-854.
[114] Celli J P, Spring B Q, Rizvi I, et al. Imaging and Photodynamic Therapy:Mechanisms, Monitoring, and Optimization[J]. Chemical Reviews,2010,110（5）：2795-2838.
[115] Alvarez-Lorenzo C, Bromberg L, Concheiro A. Light-Sensitive IntelligentDrug Delivery Systems[J]. Photochemistry and Photobiology,2009,85（4）：848-860.
[116] Young S W, Qing F, Harriman A, et al. Gadolinium (III) Texaphyrin: a TumorSelective Radiation Sensitizer that is Detectable by MRI[J]. Proceedings of theNational Academy of Sciences,1996,93（13）：6610-6615.
[117] Hofmann B, Bogdanov A, Marecos E, et al. Mechanism of Gadophrin-2Accumulation in Tumor Necrosis. Journal of Magnetic Resonance Imaging[J].1999,9（2）：336-341.
[118] Li G L, Slansky A, Dobhal M P, et al. Chlorophyll-a Analogues Conjugatedwith Aminobenzyl-DTPA as Potential Bifunctional Agents for MagneticResonance Imaging and Photodynamic Therapy[J]. Bioconjugate Chemistry,2005,16（1）：32-42.
[119] Spernyak J A, White W H, Ethirajan M, et al. Hexylether Derivative ofPyropheophorbide-A (HPPH) on Conjugating With3gadolinium(III)Aminobenzyldiethylenetriaminepentaacetic Acid Shows Potential for in VivoTumor Imaging (MR, Fluorescence) and Photodynamic Therapy[J].Bioconjugate Chemistry,2010,21（5）：828-835.
[120] Mosmann T. Rapid Colorimetric Assay for Cellular Growth and Survival:Application to Proliferation and Cytotoxicity Assays[J]. Journal ofImmunological Methods,1983,65：55-63.
[121] He Q, Shi J. Mesoporous Silica Nanoparticle Based Nano Drug DeliverySystems: Synthesis, Controlled Drug Release and Delivery, Pharmacokineticsand Biocompatibility[J]. Journal of Materials Chemistry,2011,21（16）：5845-5855.
[122] Vivero-Escoto J L, Slowing I I, Trewyn B G, et al. Mesoporous SilicaNanoparticles for Intracellular Controlled Drug Delivery[J]. Small,2010,6（18）：1952-1967.
[123] Wang X, Yang L, Chen Z G, et al. Application of Nanotechnology in CancerTherapy and Imaging[J]. A Cancer Journal for Clinicians,2008,58（2）：97-110.
[124] Zamboni W C. Liposomal, Nanoparticle, and Conjugated Formulations ofAnticancer Agents[J]. Clinical Cancer Research,2005,11（23）：8230-8234.
[125] Li S D, Chen Y C, Hackett M J, et al. Tumor-targeted Delivery of SiRNA bySelf-assembled Nanoparticles[J]. Molecular Therapy,2008,16（1）：163-169.
[126] Anderson P M, Hanson D C, Hasz D E, et al. Cytokines in Liposomes:Preliminary Studies with IL-1, IL-2, IL-6, GM-CSF and Interferongamma[J].Cytokines,1994,6（1）：92-101.
[127] Ye Q, Asherman J, Stevenson M, et al. DepoFoam Technology: a Vehicle forControlled Delivery of Protein and Peptide Drugs[C]. Journal of ControlledRelease,2000,64（1-3）：155-166.
[128] Cullis P R, Hope M J, Bally M B, et al. Influence of pH Gradients on the TransBilayer Transport of Drugs, Lipids, Peptides and Metal Ions into LargeUnilamellar Vesicles[J]. Biochimica et Biophysica Acta,1997,1331（2）：187-211.
[129] Huang C H. Phosphatidylcholine Vesicles. Formation and PhysicalCharacteristics[J]. Biochemistry,1969,8：344-352.
[130] Anzai J-I, Osa T. Photosensitive Artificial Membranes Based on Azobenzeneand Spirobenzopyran Derivatives[J]. Tetrahedron,1994,50（14）：4039-4070.
[131] Ma Y, Dai Z, Gao Y, et al. Liposomal Architecture Boosts Biocompatibility ofNanohybrid Cerasomes. Nanotoxicology[J].2011,5（4）：622-635.
[132] Wu Y, Demachi Y, Tsutsumi O, et al. Photoinduced Alignment of PolymerLiquid Crystals Containing Azobenzene Moieties in the Side Chain.3. Effectof Structure of Photochromic Moieties on Alignment Behavior[J].Macromolecules,1998,31（14）：4457-4463.
[133] Park C, Lim J, Yun M, et al. Photoinduced Release of Guest Molecules bySupramolecular Transformation of Self-assembled Aggregates Derived fromDendrons[J]. Angewandte Chemie International Edition,2008,47（16）：2959-2963.
[134] Gillies E R, Jonsson T B, Fréchet J M J. Stimuli-Responsive SupramolecularAssemblies of Linear-Dendritic Copolymers[J]. Journal of the AmericanChemical Society,2004,126（38）：11936-11943.
[135] Angelos S, Yang Y-W, Khashab N M, et al. Dual-Controlled NanoparticlesExhibiting AND Logic[J]. Journal of the American Chemical Society,2009,131（32）：11344-11346.
[136] Chen B, Pogue B W, Hasan T. Liposomal Delivery of PhotosensitisingAgents[J]. Expert Opinion on Drug Delivery,2005,2（3）：477-487.
[137] Roy I, Ohulchanskyy T Y, Pudavar H E, et al. Ceramic-Based NanoparticlesEntrapping Water-Insoluble Photosensitizing Anticancer Drugs: A Novel Drug-Carrier System For Photodynamic Therapy[J]. Journal of the AmericanChemical Society,2003,125（26）：7860-7865.
[138] Ohulchanskyy T Y, Roy I, Goswami L N, et al. Organically Modified SilicaNanoparticles with Covalently Incorporated Photosensitizer for PhotodynamicTherapy of Cancer[J]. Nano Letters,2007,7（9）：2835-2842.
[139] van Nostrum C F. Polymeric Micelles to Deliver Photosensitizers forPhotodynamic Therapy[J]. Advanced Drug Delivery Reviews,2004,56（1）：9-16.
[140] Wang S, Gao R, Zhou F, et al. Nanomaterials and Singlet OxygenPhotosensitizers: Potential Applications in Photodynamic Therapy[J]. Journalof Materials Chemistry,2004,14（4）：487-493.
[141] Gao D, Agayan R R, Xu H, et al. Nanoparticles for Two-photon PhotodynamicTherapy in Living Cells[J]. Nano Letters,2006,6（11）：2383-2386.
[142] Derycke A S L, deWitte P A M. Liposomes for Photodynamic Therapy[J].Advanced Drug Delivery Reviews,2004,56（1）：17-30.
[143] Lovell J F, Jin C S, Huynh E, et al. Porphysome Nanovesicles Generated byPorphyrin Bilayers for Use as Multimodal Biophotonic Contrast Agents[J].Nature Materials,2011,10（4）：324-332.
[144] Lindig B A, Rodgers M A J, Schaap A P. Determination of the Lifetime ofSinglet Oxygen in D2O Using9,10-Anthracenedipropionic Acid, a Water-Soluble Probe[J]. Journal of the American Chemical Society,1980,102（17）：5590-5593.
[145] Dzwigaj S, Pezerat H. Singlet Oxygen-trapping Reaction as a Method of1O2detection: role of some reducing agents[J]. Free Radical Research,1995,23（2）：103-115.
[146] Guelluy P-H, Fontaine-Aupart M-P, Grammenos A, et al. OptimizingPhotodynamic Therapy by Liposomal Formulation of the PhotosensitizerPyropheophorbide-a Methyl Ester: in Vitro and ex Vivo ComparativeBiophysical Investigations in a Colon Carcinoma Cell Line[J]. Photochemistryand Photobiology,2010,9（9）：1252-1260.
[147] Huang X L, Teng X, Chen D, et al. The Effect of the Shape of MesoporousSilica Nanoparticles on Cellular Uptake and Cell Function[J]. Biomaterials,2010,31（3）：438-448.
[148] Ideta R, Tasaka F, Jang W-D, et al. Nanotechnology-Based PhotodynamicTherapy for Neovascular Disease using a Supramolecular Nanocarrier loadedwith a Dendritic Photosensitizer[J]. Nano Letters,2005,5（12）：2426-2431.
[149] Pan D, Caruthers S D, Senpan A, et al. Revisiting an Old Friend: Manganese-based MRI Contrast Agents[J]. WIREs Nanomedicine and Nanobiotechnology,2011,3（2）：162-173.
[150] Zhang X A, Lovejoy K S, Jasanoff A, et al. Water-soluble Porphyrins as aDual-Function Molecular Imaging Platform for MRI and Fluorescence ZincSensing[J]. Proceedings of the National Academy of Sciences,2007,104（26）：10780-10785.
[151] Chen C W, Cohen J S, Myers C E, et al. Paramagnetic Metalloporphyrins asPotential Contrast Agents in NMR Imaging[J]. FEBS Letters,1984,168:70-74.
[152] Koenig S H, Brown R D,3rd, et al. The Anomalous Relaxivity of Mn3+(TPPS4)[J]. Magnetic Resonance in Medicine,1987,4（3）：252-260.
[153] Fiel R J, Button T M, Gilani S, et al. Proton Relaxation Enhancement byManganese (III) TPPS4in a Model Tumor System[J]. Magnetic ResonanceImaging,1987,5（2）：149-156.
[154] Lyon R C, Faustino P J, Cohen J S, et al. Tissue Distribution and Stability ofMetalloporphyrin MRI Contrast Agents[J]. Magnetic Resonance in Medicine,1987,4（1）：24-33.
[155] Woodburn K W. Intracellular Localization of the Radiation EnhancerMotexafin Gadolinium using Interferometric Fourier FluorescenceMicroscopy[J]. Journal of Pharmacology and Experimental Therapeutics,2001,297（3）：888-894.
[156] Zhang Z, He R, Yan K, et al. Synthesis and In Vitro and In Vivo Evaluation ofManganese (III) Porphyrin–Dextran as a Novel MRI Contrast Agent[J].Bioorganic&Medicinal Chemistry Letters,2009,19（23）：6675-6678.