含环糊精聚合物体系的构建及其生物应用研究
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摘要
环糊精(CD)是由6~8个吡喃葡萄糖单元通过α-1,4糖苷键链接起来的环状分子,呈两端开口的中空桶状立体结构,具有腔内疏水、腔外亲水的两亲性特点,可以通过主客体相互作用包结多种客体分子,形成环糊精复合物。与此同时,环糊精分子含有多个反应活性不同的羟基,可以通过改性修饰制备新型环糊精化合物。由于具有较低的生物毒性和较好的生物安全性,近年来环糊精在药物控制释放、非病毒基因载体、食品添加剂、化妆品等领域得到广泛应用。将环糊精通过非共价或共价方式引入聚合物中,可获得兼具环糊精和聚合物性能优势的含环糊精聚合物体系。本文利用主客体相互作用、迈克尔加成聚合等方法制备了一系列含环糊精聚合物体系,并对其作为药物或基因载体的生物应用进行了评估。具体研究内容和主要结论如下:
     1.环糊精/聚丙烯酸/聚乙二醇三元复合物的制备、表征及其作为药物载体的评估
     聚丙烯酸(PAA)和聚乙二醇(PEG)通过氢键作用可以形成聚合物复合物,在其稀溶液中加入不同量的β-环糊精(β-CD),得到了一系列具有不同粒子尺寸的三元复合物溶液。β-环糊精的含量越高,纳米粒子的尺寸越小。用动态光散射、透射电子显微镜、核磁共振扩散技术、固体核磁共振以及红外光谱技术对上述体系进行了结构表征,证实了体系中存在主客作用和氢键作用的相互竞争,导致粒子尺寸随β-环糊精含量发生变化。3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)方法测试细胞毒性的结果表明,β-CD/PAA/PEG三元复合物具有较低的细胞毒性。流式细胞仪和激光共聚焦显微镜分析显示,装载抗癌药物阿霉素(DOX)的β-CD/PAA/PEG三元复合物能够高效地被细胞摄入,MTT药效测试结果表明其对人宫颈癌细胞(Hela细胞)的生长有一定的抑制效果。因此,β-CD/PAA/PEG三元复合物可能成为一类有前景的药物载体材料。
     2.环糊精/超支化多臂星型聚合物刷超分子水凝胶的制备和载药性能研究
     以超支化双硫酯为链转移剂、偶氮二异丁腈(AIBN)为引发剂,进行甲基丙烯酸聚乙二醇酯(PEGMA)的可逆加成-断裂链转移(RAFT)聚合,合成了超支化多臂星型聚合物刷。利用超支化多臂星型聚合物刷上的聚乙二醇链段和α-环糊精之间的包结作用制备了一种具有温度响应性的超分子水凝胶。用红外光谱、核磁共振和广角X射线衍射等方法对水凝胶的结构和成胶机理进行了研究,并通过MTT方法对其细胞毒性进行了评估。采用这种超分子水凝胶负载了抗癌药物DOX,载药释放研究结果表明,DOX药物释放时间可持续数十天。这些性能证明环糊精/超支化多臂星型聚合物刷超分子水凝胶可作为一种潜在的可注射药物释放体系应用到癌症治疗领域。
     3.含环糊精超支化聚酰胺胺的合成及其基因输送体系的构建
     通过迈克尔加成聚合,以N, N'-亚甲基双丙烯酰胺、1-(2-胺乙基)哌嗪和单胺基修饰的β-环糊精为单体,在水中一步合成制备得到了含环糊精超支化聚酰胺胺。采用核磁共振、红外光谱、凝胶渗透色谱、酸碱滴定、琼脂糖凝胶电泳等技术,对所得聚合产物的结构和性能进行了详细表征。结果表明,通过调节投料比得到了一系列具有不同环糊精含量的超支化聚合物,其支化度在0.30~0.34,数均分子量为9,500~14,000。用MTT方法评价了含环糊精超支化聚酰胺胺的细胞毒性,结果显示环糊精含量的增加有助于降低材料的毒性。含环糊精超支化聚酰胺胺具有良好的质子缓冲能力,能够有效压缩质粒DNA,在无血清和有血清条件下均能进行高效基因转染,环糊精的含量对基因转染效率影响不明显。
     4.含环糊精超支化聚酰胺胺的荧光性能及基因转染过程示踪
     利用荧光光谱技术系统表征了含环糊精超支化聚酰胺胺的荧光性能。结果表明此类聚合物具有很宽的荧光发射谱,几乎覆盖整个可见光区。聚合物的荧光强度与温度和pH相关。更为重要的是,随着环糊精含量的增加,聚合物的荧光强度大为增强,荧光寿命和量子产率也略有增大。示差扫描量热分析结果显示,随着环糊精含量的增加,聚合物的玻璃化转变温度升高,这可能是大体积的β-环糊精使得聚合物变得更加刚性所致。利用含环糊精超支化聚酰胺胺的荧光性能,无需添加荧光标记物,用流式细胞仪和激光共聚焦显微镜跟踪了其与质粒DNA复合后进入细胞、介导基因转染的过程,结果显示聚合物/质粒DNA的复合物可以高效进入细胞,聚合物载体在转染过程中停留在细胞质内。
Cyclodextrins (CDs) are a series of natural cyclic oligosaccharides composed of α-1,4-coupled D-glucose units. The most commonly used CD subtypes are α-CD, β-CD andγ-CD, which consist of6,7,8D-glucose units, respectively. CDs display a bucket-likestructure with a hydrophobic inner cavity that can form inclusion complexes with variousguest molecules, including many kinds of polymers. Meanwhile, abundant hydroxylslocated on the hydrophilic exterior of CDs show varied reactivity, which make it easy tosynthesize modified CDs. CDs have often been used to design and construct polymericmaterials by host-guest interactions or covalent modifications. CD-based polymericmaterials usually exhibit unique characteristics in terms of mechanical properties,stimuli-responsiveness, good availability, etc., facilitating their wide applications in drugdelivery, gene transfection, food additives, flavoring materials and cosmetics.
     In this dissertation, we designed and constructed several CD-based polymericsystems through host-guest interaction or by Michael addition reaction. The chemicalstructures and properties of these systems were thoroughly characterized, and theapplications in drug and gene delivery of these systems were also estimated. The detailsand key conclusions are described as follows:
     1. Construction of interpolymer complexes with controlling particle size throughhost-guest interaction for drug delivery
     A new method to adjust the particle size of interpolymer complexes was developedby introduction of host-guest interaction into the dilute aqueous solution of poly(acrylicacid)(PAA) and poly(ethylene glycol)(PEG). Due to the cooperative hydrogen-bondinginteraction, PAA formed the interpolymer complexes with PEG. Adding β-CD into dilutePAA/PEG aqueous solution, the competition between host-guest and hydrogen-bondinginteractions happened. The β-CD/PAA/PEG ternary systems were well characterized byultraviolet-visible absorption spectroscopy (UV-Vis), dynamic light scattering (DLS),transmission electron microscopy (TEM), diffusion NMR spectroscopy, Fourier transforminfrared (FTIR) and solid-state13C NMR spectroscopy. The results indicated that thehydrophobic cavity of β-CD was threaded by linear polymers so that the hydrophilicity ofPAA/PEG interpolymer complexes was improved greatly. Adjusting the amounts of β-CD,the particle size of the interpolymer complexes could be readily controlled. The lowcytotoxicity of various β-CD/PAA/PEG ternary complexes was confirmed using the MTTassay in COS-7cell line. Doxorubicin (DOX), an anticancer drug, was encapsulated intothe β-CD/PAA/PEG ternary complexes. The DOX-loaded β-CD/PAA/PEG ternarycomplexes had been analyzed by flow cytometry (FCM) analysis, confocal laser scanningmicroscopy (CLSM) and the methyl tetrazolium (MTT) assay against human cervicalcarcinoma cell (Hela). The results indicated that β-CD/PAA/PEG ternary complexes withcontrolled particle size could be used as safe and promising drug carriers.
     2. Preparation and characterization of supramolecular hydrogel consisting of adendritic multiarm copolymer brush and α-CDs for drug delivery
     Through reversible addition-fragmentation transfer (RAFT) polymerization ofpoly(ethylene glyco1) methyl ether methacrylate (PEGMA) initiated by dendritic macroinitiator, a dendritic multiarm copolymer brush was successfully synthesized.Benefiting from the cooperation of host-guest interaction and hydrogen-bondinginteraction, a supramolecular hydrogel formed between the dendritic multiarm copolymerbrush and α-CDs in an aqueous solution. The resultant hydrogel showed uniquetemperature-dependent sol-gel phase transition. The structure and the forming mechanismof the supramolecular hydrogel were characterized by FTIR、NMR and X-ray diffraction(XRD) techniques. MTT assay in NIH-3T3cell line proved the low cytotoxicity of thehydrogel. The anticancer drug DOX could be loaded into the hydrogel, and theencapsulated DOX could be released gradually in a long time. It suggested that thissupramolecular hydrogel consisting of a dendritic multiarm copolymer brush and α-CDscould be useful as an injectable drug delivery system.
     3. Design and synthesis of hyperbranched poly(amido amine) containing β-CDs as anonviral gene delivery vector
     Hyperbranched poly(amido amine) containing different amounts of β-CDs(HPAMAM-CDs) were synthesized through a simple and efficient one-step Michaeladdition copolymerization of N, N’-methylenebis(acrylamide)(MBA),1-(2-aminoethyl)piperazine (AP) and mono-6-dexy-6-ethylenediamino-β-CD (EDA-β-CD). NMR, GPC(gel permeation chromatography), and FTIR techniques were used to characterize thestructure of the obtained HPAMAM-CDs. MTT assay proved that the cytotoxicity becamelower as the β-CD content increased. The agarose gel electrophoresis results indicated thatHPAMAM-CDs could condense pDNA very well. In vitro transfection evaluation ofHPAMAM-CD/pDNA complexes in the absence or presence of10%FBS showed highgene transfection efficiencies. Furthermore, the inner cavities of β-CDs inHPAMAM-CDs could be used to encapsulate drugs through host-guest interaction.Therefore, the HPAMAM-CDs may have potential application in the combination of genetherapy and chemotherapy.
     4. Fluorescence properties of HPAMAM-CDs and their application as fluorescenttracker in gene transfection process
     HPAMAM and HPAMAM-CDs were found to display fluorescence with theemission bands of nearly whole visible wavelength range. In comparison to pureHPAMAM, the fluorescence intensity of HPAMAM-CDs was enhanced significantly. Thefluorescence enhancement of HPAMAM-CDs might result from the restricted rotationalmotion of the terminal chains caused by the steric hindrance of big β-CD units, which wasconfirmed by the differential scanning calorimeter (DSC) results. Benefiting from thestrong fluorescence of HPAMAM-CD, the cell internalization studies ofHPAMAM-CD/pDNA complexes were preformed conveniently without fluorescentlabeling. FCM and CLSM results demonstrated that the cellular uptake ofHPAMAM-CD/pDNA complexes was very fast and HPAMAM-CDs mainly located inthe cytoplasm of the cells during the gene transportation process.
引文
[1] Szetjli, J. Introduction and General Overview of Cyclodextrin Chemistry. Chem. Rev.1998,98,1743-1753.
    [2]童林荟,《环糊精化学-基础与应用》,北京,科学出版社,2001.
    [3] van de Manakker, F.; Vermonden, T.; van Nostrum, C. F.; Hennink, W. E. Cyclodextrin-basedpolymeric materials: synthesis, properties, and pharmaceutical/biomedical applications.Biomacromolecules2009,10,3157-3175.
    [4]陈亮,环糊精与超支化聚合物超分子体系的设计、合成与控制,[博士论文],上海,上海交通大学,2006.
    [5] Szejtli, J. Cyclodextrin technology, Kluwer, Dordrecht,1988.
    [6] Rajewski, R. A.; Stella, V. Pharmaceutical applications of cyclodextrins.2. in vivo drug delivery. J.Pharm. Sci.1996,85,1142-1169.
    [7] Wenz, G.; Han, B. H.; Müller, A. Cyclodextrin rotaxanes and polyrotaxanes. Chem. Rev.2006,106,782-817.
    [8] Loftsson, T.; Masson, M.; Brewster, M. E. Self-association of cyclodextrins and cyclodextrincomplexes. J. Pharm. Sci.2004,93,1091-1099.
    [9] Uekama, K.; Hirayama, F.; Irie, T. Cyclodextrin drug carrier systems. Chem. Rev.1998,98,2045-2076.
    [10] Shimpi, S.; Chauhan, B.; Shimpi, P. Cyclodextrins: application in different routes of drugadministration. Acta. Pharm.2005,55,139-156.
    [11] Varca, G. H. C.; Andreo-Filho, N.; Lopes, P. S.; Ferraz, H. G. Cyclodextrins: an overview of thecomplexation of pharmaceutical proteins. Curr.Protein Pep.Sci.,2010,11,255-263.
    [12] Engeldinger, E.; Armspach, D.; Matt, D. Capped cyclodextrins. Chem. Rev.2003,103,4147-4173.
    [13] Khan, A. R.; Forgo, P.; Stine, K. J.; D'Souza, V. T. Methods for selective modifications ofcyclodextrins. Chem. Rev.1998,98,1977-1996.
    [14] Loftsson, T.; Duchene, D. Cyclodextrins and their pharmaceutical applications. Int. J. Pharm.2007,329,1-11.
    [15] Vyas, A.; Saraf, S.; Saraf, S. Cyclodextrin based novel drug delivery systems. J. Incl. Phenom.Macrocycl. Chem.2008,62,23-42.
    [16] Davis, M. E.; Brewster, M. E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev.Drug. Discov.2004,3,1023-1035.
    [17] Stella, V. J.; He, Q. Cyclodextrins. Toxicol. Pathol.2008,36,30-42.
    [18] Harada, A.; Kamachi, M. Complex formation between poly(ethy1ene glycol) and α-cyclodextrin.Macromolecules1990,23,2821-2823.
    [19] Huang, L.; Allen, E.; Tonelli, A. E. Study of the inclusion compounds formed betweenα-cyclodextrin and high molecular weight poly(ethylene oxide) and poly(ε-caprolactone). Polymer1998,39,4857-4865.
    [20] Harada, A. Preparation and structures of supramolecules between cyclodextrins and polymers.Coord. Chem. Rev.1996,148,115-133.
    [21] Harada, A.; Okada, M.; Li, J.; Kamachi, M. Preparation and characterization of inclusioncomplexes of poly(propylene glycol) and cyclodextrins. Macromolecules1995,28,8406-8411.
    [22] Harada, A.; Li, J.; Kamachi, M. Complex formation between poly(methyl vinyl ether) andγ-cyclodextrin. Chem.Lett.1993,22,237-240.
    [23] Harada, A.; Li, J.; Kamachi, M. Double-stranded inclusion complexes of cyclodextrin threaded onpoly(ethylene glycol). Nature1994,370,126-128.
    [24]李景烨,环糊精与聚合物的结晶内含复合物的研究,[博士论文],上海,上海交通大学,2002.
    [25] Jiang, Y.; Wu, J. L.; He, L.; Tu, C. L.; Zhu, X. Y.; Chen, Q.; Yao, Y. F.; Yan, D. Y. Construction ofpolyrotaxanes via reversible chain exchange between acylhydrazone bonds. Chem. Commun.2008,47,6351-6353.
    [26] Li, J.; Ni, X. P.; Leong, K. W. Block-selected molecular recognition and formation ofpolypseudorotaxanes between poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide)triblock copolymers and α-cyclodextrin. Angew. Chem. Int. Ed.2003,42,69-72.
    [27] Li, J.; Ni, X. P.; Zhou, Z. H.; Leong, K. W. Preparation and characterization ofpolypseudorotaxanes based on block-selected inclusion complexation between poly(propyleneoxide)-poly(ethylene oxide)-poly(propylene oxide) triblock copolymers and α-cyclodextrin. J. Am.Chem. Soc.2003,125,1788-1795.
    [28] Dai, X. H.; Dong, C. M.; Fa, H. B.; Yan, D. Y. Wei, Y. Supramolecular polypseudorotaxanescomposed of star-shaped porphyrin-cored poly(ε-caprolactone) and α-cyclodextrin.Biomacromolecules2006,7,3527-3533.
    [29] He, L. H.; Huang, J.; Chen, Y. M.; Liu, L. P. Inclusion complexation between comblike PEOgrafted polymers and α-cyclodextrin. Macromolecules2005,38,3351-3355.
    [30] Zhu, X. Y.; Chen, L.; Yan, D. Y.; Chen, Q.; Yao, Y. F.; Xiao, Y. Hou, J. Li, J. Y. Supramolecularself-assembly of inclusion complexes of a multiarm hyperbranched polyether with cyclodextrins.Langmuir2004,20,484-490.
    [31] Li, J.; Harada, A.; Kamachi, M. Sol-gel transition during inclusion complex formation betweenα-cyclodextrin and high-molecular-weight poly(ethylene glycol)s in aqueous solution. Polym J,1994,26,1019-1026.
    [32] Liao, X. J.; Chen, G. S.; Liu, X. X.; Chen, W. X.; Chen, F. E.; Jiang, M. Photoresponsivepseudopolyrotaxane hydrogels based on competition of host-guest interactions. Angew. Chem. Int.Ed.2010,49,4409-4413.
    [33] Li, L.; Guo, X.; Wang, J.; Liu, P.; Prud’homme, R. K.; May, B. L.; Lincoln, S. F. Polymer networksassembled by host-guest inclusion between adamantyl and β-cyclodextrin substituents onpoly(acrylic acid) in aqueous solution. Macromolecules2008,41,8677-8681.
    [34] Wang, J.; Jiang, M. Polymeric self-assembly into micelles and hollow spheres with multi-scalecavities driven by inclusion complexation. J. Am. Chem. Soc.2006,128,3703-3708.
    [35] Harada, A.; Furue, M.; Nozakura, S. Cyclodextrin-containing polymers.1. Preparation of polymers.Macromolecules1976,9,701-704.
    [36] Harada, A.; Furue, M.; Nozakura, S. Interaction of cyclodextrin-containing polymers withfluorescent compounds. Macromolecules1976,10,676-681.
    [37] Zhong, N.; Byun, H. S.; Bittman, R. Hydrophilic cholesterol-binding molecular imprintedpolymers. Tetra. Lett.2001,42,1839-1841.
    [38] Liu, Y. Y.; Fan, X. D.; Gao, L. Synthesis and characterization of β-Cyclodextrin based functionalmonomers and its copolymers with N-isopropylacrylamide。Macromol. Biosci.2003,3,715-719.
    [39] Tian, W.; Fan, X. D.; Kong, J.; Liu, T.; Liu, Y. Y.; Huang, Y.; Wang, S. J.; Zhang, G. B.Cyclodextrin-based hyperbranched polymers: molecule design, synthesis, and characterization.Macromolecules2009,42,640-651.
    [40] Vélaz, I.; Isasi, J. R.; Sánchez, M.; Uzqueda, M.; Ponchel, G. Structural characteristics of somesoluble and insoluble β-cyclodextrin polymers. J. Inclusion Phenom. Macrocyclic Chem.2007,57,65-68.
    [41] Renard, E.; Barnathan, G.; Deratani, A.; Sébille, B. Polycondensation of cyclodextrins withepichlorohydrin. Influence of reaction conditions on the polymer structure. Macromol. Symp.1997,122,229-234.
    [42] Renard, E.; Volet, G.; Deratani, A.; Sébille, B. Preparation and characterization of water solublehigh molecular weight β-cyclodextrin-epichlorohydrin polymers. Eur. Polym. J.1997,33,49-57.
    [43] Murai, S.; Imajo, S.; Maki, Y.; Takahashi, K.; Hattori, K. Adsorption and recovery of nonionicsurfactants by β-cyclodextrin polymer. J. Colloid Interface Sci.1996,183,118-123.
    [44] Gu, T.; Tsai, G.-J.; Tsao, G. T. Synthesis of rigid cyclodextrin-containing polymeric resins foradsorption. J. Inclusion Phenom. Macrocyclic Chem.2006,56,375-379.
    [45] Girek, T.; Shin, D.-H.; Lim, S.-T. Polymerization of β-cyclodextrin with maleic anhydride andstructural characterization of the polymers. Carbohydr. Polym.2000,42,59-63.
    [46] Girek, T.; Kozlowski, C. A.; Koziol, J. J.; Walkowiak, W.; Korus, I. Polymerisation ofβ-cyclodextrin with succinic anhydride. Synthesis, characterisation, and ion flotation of transitionmetals. Carbohydr. Polym.2005,59,211-215.
    [47] Ma, M.; Li, D. New organic nanoporous polymers and their inclusion complexes. Chem. Mater.1999,11,872-874.
    [48] Binello, A.; Robaldo, B.; Barge, A.; Cavalli, R.; Cravotto, G. Synthesis of cyclodextrin-basedpolymers and their use as debittering agents J. Appl. Polym. Sci.2008,107,2549-2557.
    [49] Cserhati, T.; Fenyvesi, E.; Szejtli, J. Interaction of nonylphenyl and tributylphenyl ethylene oxideionic surfactants with highly soluble cyclodextrin derivatives. J. Inclusion Phenom. Mol. Recognit.Chem.1992,14,181-188.
    [50] Inoue, Y.; Miyauchi, M.; Nakajima, H.; Takashima, Y.; Yamaguchi, H.; Harada, A. Self-threadingof a poly(ethylene glycol) chain in a cyclodextrin-ring: control of the exchange dynamics by chainlength. J. Am. Chem. Soc.2006,128,8994-8995.
    [51] Seo, T.; Kajihara, T.; Iijima, T. The synthesis of poly(allklamine) containing covalently bondcyclodextrin and its catalytic effect in the hydrolysis of phenyl esters. Makromol. Chem.1987,188,2071-2082.
    [52] Ruebner, A.; Statton, G. L.; James, M. R. Synthesis of a linear polymer with pendentγ-cyclodextrin. Macromol. Chem. Phys.2000,201,1185-1188.
    [53] Tojima, T.; Katsura, H.; Han, A. M.; Tanida, F.; Nishi, N.; Tokura, S.; Sakairi, N. Preparation of acyclodextrin-linked chitosan derivative via reductive amination strategy. J. Polym. Sci. Part A:Polym. Chem.1998,36,1965-1968.
    [54] Tanida, F.; Tojima, T.; Han, S. M.; Nishi, N.; Tokura, S.; Sakairi, N.; Seino, H.; Hamada, K. Novelsynthesis of a water-soluble cyclodextrin-polymer having a chitosan skeleton. Polymer1998,39,5261-5263.
    [55] Chen, S. P.; Wang, Y. T.; Study on β-cyclodextrin grafting with chitosan and slow release of itsinclusion complex with radioactive iodine. J. Appl. Polym. Sci.2001,82,2414-2421.
    [56] Martel, B.; Devassine, M.; Crini, G.; Weltrowski, M.; Bourdonneau, M.; Morcellet, M. Preparationand sorption properties of a β-cyclodextrin-linked chitosan derivative. J. Polym. Sci. Part A: Polym.Chem.2001,39,169-176.
    [57] Gaffar, M. A.; El-Rafie, S. M. El-Tahlawy, K. F. Preparation and utilization of ionic exchangeresin via graft copolymerization of β-CD itaconate with chitosan. Carbohydr. Polym.2004,56,387-396.
    [58] El-Tahlawy, K. Gaffar, M. A.; El-Rafie, S. Novel method for preparation of β-cyclodextrin/graftedchitosan and it’s application. Carbohydr. Polym.2006,63,385-392.
    [59] Huh, K. M.; Tomita, H.; Lee, W. K.; Oaya, T.; Yui, N. Synthesis of α-cyclodextrin-conjugatedpoly(ε-lysine)s and their inclusion complexation behavior. Macromol. Rapid Commun.2002,23,179-182.
    [60] Choi, H. S.; Huh, K. M. Ooya, T. Yui, N. pH-and thermosensitive supramolecular assemblingsystem: rapidly responsive properties of β-cyclodextrin-conjugated poly(ε-lysine). J. Am. Chem.Soc.2003,125,6350–6351.
    [61] Takashima, Y.; Osaki, M.; Harada, A. Cyclodextrin-initiated polymerizationof cyclic esters in bulk:formation of polyester-tethered cyclodextrins. J. Am. Chem. Soc.2004,126,13588-13589.
    [62] Chen, L.; Zhu, X. Y.; Yan, D. Y. Synthesis and characterization of hyperbranchedpoly(sulfone-amine) modified β-cyclodextrin. E-polymers2006,045.
    [63] Xu, F. J.; Zhang, Z. X.; Ping, Y.; Li, J.; Kang, E. T.; Neoh, K. G. Star-shaped cationic polymers byatom transfer radical polymerization from β-cyclodextrin cores for nonviral gene delivery.Biomacromolecules2009,10,285-293.
    [64] Li, J.; Loh, X. J. Cyclodextrin-based supramolecular architectures: syntheses, structures, andapplications for drug and gene delivery. Adv. Drug Deliv. Rev.2008,60,1000-1017.
    [65] Li, J.; Ni, X. P.; Leong, K. W. Injectable drug-delivery systems based on supramolecular hydrogelsformed by poly(ethylene oxide) and alpha-cyclodextrin. J. Biomed. Mater. Res. Part A2003,65A,196-202.
    [66] Li, X.; Li, J. Supramolecular hydrogels based on inclusion complexation between poly(ethyleneoxide)-b-poly(ε-caprolactone) diblock copolymer and α-cyclodextrin and their controlled releaseproperty. J. Biomed. Mater. Res. Part A2008,86A,1055-1061.
    [67] Ni, X. P.; Cheng, A.; Li, J. Supramolecular hydrogels based on self-assembly betweenPEO-PPO-PEO triblock copolymers and α-cyclodextrin. J. Biomed. Mater. Res. Part A2009,88A,1031-1036.
    [68] Li, J.; Ni, X. P.; Wang, X.; Li, H. Z.; Leong, K. W. Self-assembled supramolecular hydrogelsformed by biodegradable PEO-PHB-PEO triblock copolymers and α-cyclodextrin for controlleddrug delivery. Biomaterials2006,27,4132-4140.
    [69] Chen, Y.; Pang, X. H.; Dong, C. M. Dual stimuli-responsive supramolecular polypeptide-basedhydrogel and reverse micellar hydrogel mediated by host–guest chemistry. Adv. Funct. Mater.2010,20,579-586.
    [70] Dong, H. Q.; Li, Y. Y.; Cai, S. J.; Zhuo, R. X. Zhang, X. Z.; Liu, L. J. A facile one-pot constructionof supramolecular polymer micelles from α-cyclodextrin and poly(ε-caprolactone). Angew. Chem.Int. Ed.2008,47,5573-5576.
    [71] Zhang, X. W.; Ke, F. Y.; Han, J.; Ye, L.; Chen, E. Q.; Zhang, A. Y.; Feng, Z. G. Theself-aggregation behaviour of amphotericin B-loaded polyrotaxane-basedtriblock copolymers andtheir hemolytic evaluation. Soft Matter2009,50,4343-4351.
    [72] Szeman, J.; Fenyvesi, E.; Szejtli, J. Water soluble cyclodextrin polymers: their interaction withdrugs. J. Incl. Phenom.1987,5,427-431.
    [73] Fenyvesi, E. Cyclodextrin polymers in the pharmaceutical industry. J. Incl. Phenom.1988,6,537-545.
    [74] Mura, P.; Faucci, M. T.; Maestrelli, F.; Furlanetto, S.; Pinzauti, S. Characterization ofphysicochemical properties of naproxen systems with amorphous β-cyclodextrin-epichlorohydrinpolymers. J. Pharm. Biomed. Anal.2002,29,1015-1024.
    [75] Li,J. S.; Xiao, H. N.; Li, J. H.; Zhong, Y. P. Drug carrier systems based on water-soluble cationicβ-cyclodextrin polymers. Int. J. Pharm.2004,278,329-342.
    [76] Fenyvesi, E.; Ujházy, A.; Szejtli, J.; Pütter, S.; Gan, T. G. Controlled release of drugs from CDpolymers substituted with ionic groups. J. Incl. Phenom. Mol. Recognit. Chem.1996,25,185-189.
    [77] Liu, Y. Y.; Fan, X. D. Synthesis and characterization of pH-and temperature-sensitive hydrogel ofN-isoplyamide/cyclodextrin based copolymer. Polymer,2002,43,4997-5003.
    [78] Liu, Y. Y.; Fan, X. D. Hu, H.; Tang, Z. H. Release of chlorambucil frompoly(N-isopropylacrylamide) hydrogels with β-cyclodextrin moieties. Macromol. Biosci.2004,4,729-736.
    [79]黄怡,范晓东,张楠楠。聚乙烯醇固载β-环糊精线性高聚物的合成及其药物控制释放研究。高分子学报2004,6,854-858。
    [80] Tian, W. Fan, X. D.; Kong, J.; Liu, Y. Y.; Zhang, W. H.; Cheng, G. W.; Jiang, M. Amphiphilichyperbranched polymers containing two types of β-cyclodextrin segments: synthesis and properties.Macromol. Chem. Phys.2009,210,2107-2117.
    [81] Zhou, Y. Y.; Guo, Z.; Zhang, Y. W.; Huang, W.; Zhou, Y. F.; Yan, D. Y. Hyperbranchedpolyamidoamines containing β-cyclodextrin for controlled release of chlorambucil. Macromol.Biosci.2009,9,1090-1097.
    [82] Gou, P. F.; Zhu, W. P.; Shen, Z. Q. Synthesis, self-assembly, and drug-loading capacity ofwell-defined cyclodextrin-centered drug-conjugated amphiphilic A14B7miktoarm star copolymersbased on poly(ε-caprolactone) and poly(ethylene glycol). Biomacromolecules2010,11,934-943.
    [83] Verma, I. M.; Somia, N. Gene therapy-promises, problems and prospects. Nature1997,389,239-242.
    [84] Anderson, W. F. Human gene therapy. Nature1998,392,25-30.
    [85] Duncan, R. The dawning era of polymer therapeutics. Nat. Rev. Drug Discov.2003,2,347-360.
    [86] Mintzer, M. A.; Simanek, E. E. Nonviral vectors for gene delivery. Chem. Rev.2009,109,259-302.
    [87] Park, T. G.; Jeong, J. H.; Kim, S. W. Current status of polymeric gene delivery systems. Adv. DrugDeliv. Rev.2006,58,467-486.
    [88] Li, S. D.; Huang, L. Non-viral is superior to viral gene delivery. J. Control. Release2007,23,181-183.
    [89] De Smedt, S. C.; Demeester, J.; Hennink, W. E. Cation polymer based gene delivery systems.Pharm. Res.2000,17,113-126.
    [90] Thomas, M.; Klibanov, A. M. Non-viral gene therapy: polycation-mediated DNA delivery. Appl.Microbiol. Biotechnol.2003,62,27-34.
    [91] Thomas, C. E.; Ehrhardt, A.; Kay, M. A. Progress and problems with the use of viral vectors forgene therapy. Nat. Rev. Genet.2003,4,346-358.
    [92] Schaffert, D.; Wagner, E. Gene therapy progress and prospects: synthetic polymer-based systems.Gene Ther.2008,15,1131-1138.
    [93] Itaka, K.; Kataoka, K. Recent development of nonviral gene delivery systems with virus-likestructures and mechanisms. Eur. J. Pharm. Biopharm.2009,71,475-483.
    [94] Wagner, E.; Kloeckner, J. Gene delivery using polymer therapeutics. Adv. Polym. Sci.2006,192,135-173.
    [95] Fischer, D.; Bieber, Y.; Li, Y. X.; Elsasser, H.-P.; Kissel, T. A novel non-viral vector for DNAdelivery based on low molecular weight, branched polyethylenimine: effect of molecular weight ontransfection efficientcy and cytotoxicity. Pharm.Res.1999,16,1273-1279.
    [96] Gosselin, M. A.; Guo, W.; Lee, R. J. Effficient gene transfer using reversibly cross-linked lowmolecular weight polyethylenimine. Bioconjug.Chem.2002,12,989-994.
    [97] Zinselmeyer, B. H.; Mackay, S. P.; Schatzlein, A. G.; Uchegbu, I. F. The lower-generationpolypropylenimine dendrimers are effective gene-transter agents. Pharm. Res.2002,19,960-967.
    [98] Wu, G. Y.; Wu, C. H. Receptor-mediated in vitro gene transformation by a soluble DNA carriersystem. J. Biol. Chem.1987,262,4429-4432.
    [99] Dekie, L.; Toncheva, V.; Dubruel, P.; Schacht, E. H.; Barrett, L.; Seymour, L. W. Poly-L-glutamicacid derivatives as vectors for gene therapy. J. Control. Release2000,65,187-202.
    [100] Qin, L. H.; Pahud, D. R.; Ding, Y. Z.; Bielinska, A. U.; Kukowska-Latallo, J. F.; Baker Jr., J. R.;Bromberget, J. S. Efficient transfer of genes into murine cardiac grafts by Starburstpolyamidoamine dendrimers. Hum. Gene Ther.1998,9,553-560.
    [101] Rudolph, C.; Lausier, J.; Naundorf, S.; Müller, R. H.; Rosenecker, J. In vivo gene delivery to thelung using polyethylenimine and fractured polyamidoamine dendrimers. J. Gene Med.2000,2,269-278.
    [102] van de Wetering, P.; Cherng, J.-Y.; Talsma, H.; Crommelin, D. J. A.; Hennink, W. E.2-(dimethylamino)ethylmethacrylate based(co)polymers as gene transfer agents. J. Control.Release1998,53,145-153.
    [103] Wang, J.; Mao, H. Q.; Leong, K. W. A novel biodegradable gene carrier based on polyphosphoester.J. Am. Chem. Soc.2001,123,9480-9481.
    [104] Kabanov, A. V.; Astafieva, I. V.; Maksimova, I. V.; Lukanidin,E. M.; Georgiev, G. P.; Kabanov, V. A.Efficient transformation of mammalian cells using DNA interpolyelectrolyte complexes withcarbon chain polycations. Bioconjug. Chem.1993,4,448-454.
    [105] Borchard, G. Chitosans for gene delivery. Adv. Drug Deliv. Rev.2001,52,145-150.
    [106] Leong, K. W.; Mao, H. Q.; Truong-Le, V. L.; Walsh, S. M. August, J. T. DNA-polycationnanospheres as non-viral gene delivery vehicles. J. Control. Release1998,53,183-193.
    [107] Shuai, X. T.; Merdan, T.; Unger, F.; Kissel, T. Supramolecular gene delivery vectors showingenhanced transgene expression and good biocompatibility. Bioconjug.Chem.2005,16,322-329.
    [108] Li, J.; Yang, C.; Li, H. Z.; Wang, X.; Goh, S. H.; Ding, J. L.; Wang, D. Y.; Leong, K. W. Cationicsupramolecules composed of multiple oligoethylenimine-grafted β-cyclodextrins threaded on apolymer chain for efficient gene delivery. Adv. Mater.2006,18,2969-2974.
    [109] Ooya, T.; Choi, H. S.; Yamashita, A. Yui, N.; Sugaya, Y. Kano, A.; Maruyama, A.; Akita, H.; Ito, R.;Kogure, K.; Harashima, H. Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced genedelivery. J. Am. Chem. Soc.2006,128,3852–3853.
    [110] Dong, R. J.; Zhou, L. Z.; Wu, J. L.; Tu, C. L.; Su, Y.; Zhu, B. S.; Gu, H. C.; Yan, D. Y.; Zhu, X. Y.A supramolecular approach to the preparation of charge-tunable dendritic polycations for efficientgene delivery. Chem. Commun.2011,47,5473-5475.
    [111] Gonzalez, H.; Hwang, S. J., Davis, M. E. New class of polymers for the delivery ofmacromolecular therapeutics. Bioconjug. Chem.1999,10,1068-1074.
    [112] Davis, M. E.; Brewster, M. E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev.Drug. Discov.2004,3,1023-1035.
    [113] Hwang, S. J.; Bellocq, N. C.; Davis, M. E. Effects of structure of α-cyclodextrin-containingpolymers on gene delivery. Bioconjug. Chem.2001,12,280-290.
    [114] Reineke, T. M.; Davis, M. E. Structural effects of carbohydrate-containing polycations on genedelivery.1. Carbohydrate size and its distance from charge centers. Bioconjug. Chem.2003,14,247-254.
    [115] Reineke, T. M.; Davis, M. E. Structural effects of carbohydrate-containing polycations on genedelivery.2. Charge center type. Bioconjug. Chem.2003,14,255-261.
    [116] Popielarski, S. R.; Mishra, S.; Davis, M. E. Structural effects of carbohydrate-containingpolycations on gene delivery.3. Cyclodextrin type and functionalization. Bioconjug. Chem.2003,14,672-678.
    [117] Pun, S. H.; Bellocq, C.; Liu, A. J. Jensen, G.; Machemer, T.; Quijano, E.; Schluep, T.; Wen, S. F.;Engler, H.; Heidel, J.; Davis, M. E. Cyclodextrin-modified polyethylenimine polymers for genedelivery. Bioconjug. Chem.2004,15,831-840.
    [118] Pun, S. H.; Davis, M. E. Development of a nonviral gene delivery vehicle for systemic application.Bioconjug. Chem.2002,13,630-639.
    [119] Tang, G. P.; Guo, H. Y.; Alexis, F.; Wang, X. Zeng, S. Lim, T. M.; Ding, J.; Yang, Y. Y.; Wang, S.Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into thenervous system. J. Gene. Med.2006,8,736-744.
    [120] Huang, H. L.; Tang, G. P.; Wang, Q. Q.; Li, D.; Shen, F. P.; Zhou, J.; Yu, H. Two novel non-viralgene delivery vectors: low molecular weight polyethylenimine cross-linked by(2-hydroxypropyl)-beta-cyclodextrin or (2-hydroxypropyl)-gamma-cyclodextrin. Chem. Commun.2006,22,2382-2384.
    [121] Haensler, J.; Szoka, F. C. Jr. Polyamidoamine cascade polymers mediate efficient transfection ofcells in culture. Bioconjug.Chem.1993,4,372-379.
    [122] Bielinska, A. U.; Chen, C.; Johnson, J.; Baker, J. R. Jr. DNA complexing with polyamidoaminedendrimers:implications for transfection. Adv. Drug Deliv. Rev.1999,10,843-850.
    [123] Braun, C. S.; Vetro, J. A.; Tomalia, D. A.; Koe, G. S. Koe, J. G. Middaugh, C. R. Structure/functionrelationships of polyamidoamine/DNA dendrimers as gene delivery vehicles. J. Pharm. Sci.2005,94,423-436.
    [124] Dennig, J. Duncan, E. Gene transfer into eukaryotic cells using activated polyamidoaminedendrimers. Rev. Mol. Biotech.2002,90,339-347.
    [125] Arima, H.; Hirayama, F.; Uekama, K. Enhancement of gene expression by polyamidoaminedendrimer conjugates with alpha-, beta-, and gamma-cyclodextrins. Bioconjug.Chem.2001,4,476-484.
    [126] Kihara, F.; Arima, H.; Tsutsumi, T.; Hirayama, F.; Uekama, K. Effects of structure ofpolyamidoamine dendrimer on gene transfer efficiency of the dendrimer conjugate withalpha-cyclodextrin. Bioconjug.Chem.2002,13,1211-1219.
    [127] Kihara, F.; Arima, H.; Tsutsumi, T.; Hirayama, F.; Uekama, K. In vitro and in vivo gene transfer byan optimized alpha-cyclodextrin conjugate with polyamidoamine dendrimer. Bioconjug.Chem.2003,14,342-350.
    [128] Arima, H.; Yunomae, K.; Morikawa, T.; Hirayama, F.; Uekama, K. Contribution of cholesterol andphospholipids to inhibitory effect of dimethylbeta-cyclodextrin on efflux function ofP-glycoprotein and multidrug resistance-associated protein2in vinblastine-resistant Caco-2cellmonolayers. Pharm. Res.2004,21,625-634.
    [129] Wada, K.; Arima, H.; Tsutsumi, T.; Chihara, Y.; Hattori, K.; Hirayama, F.; Uekama, K.Improvement of gene delivery mediated by mannosylated dendrimer/alpha-cyclodextrin conjugates.J. Control. Release2005,104,397-413.
    [130] Arima, H.; Chihara, Y.; Arizono, M.; Yamashita, S.; Wada, K.; Hirayama, F.; Uekama, K.Enhancement of gene transfer activity mediated by mannosylated dendrimer/alpha-cyclodextrinconjugate (generation3, G3) J. Control. Release2006,116,64-74.
    [131] Yang, C. A.; Li, H. Z.; Goh, S. H. Li, J. Cationic star polymers consisting of α-cyclodextrin in coreand oligoethylenimine arms as nonviral gene delivery vectors. Biomaterials2007,28,3245-3254.
    [132] Srinivasachari, S.; Fichter, K. M.; Reineke, T. M. Polycationic β-cyclodextrin “click clusters”:monodisperse and versatile scaffolds for nuclei acid delivery. J. Am. Chem. Soc.2008,130,4618–4627.
    [133] Mendez-Ardoy, A.; Guilloteau, N.; Giorgio C. D.; Vierling, P. Santoyo-Gonzalez, F.; Mellet, C. O.;Fernadarz, J. M. G. β-Cyclodextrin-Based Polycationic Amphiphilic “Click” Clusters: Effect ofStructural Modifications in Their DNA Complexing and Delivery Properties. J. Org. Chem.2011,76,5882-5894.
    [134] Bekturov, E. A.; Bimendina, L. A. Interpolymer complexes. Adv. Polym. Sci.1981,41,99-147.
    [135] Tsuchida, E.; Abe, K. Interactions Between Macromolecules in Solution and IntermacromolecularComplexes. Adv. Polym. Sci.1982,45,1-119.
    [136] Philipp, B.; Dautzenberg, H.; Linow, K. J.; K tz, J.; Dawydoff, W. Polyelectrolyte complexes-recent developments and open problems. Prog. Polym. Sci.1989,14,91-172.
    [137] Bell, C. L.; Peppas, N. A. Biomedical membranes from hydrogels and interpolymer complexes.Adv. Polym. Sci.1995,122,125-175.
    [138] Jiang, M.; Li, M.; Xiang, M. L.; Zhou, H. Interpolymer complexation and miscibility enhancementby hydrogen bonding. Adv. Polym. Sci.1999,146,121-196.
    [139] Thünemann, A. Polyelecrolyte-surfactant complexes (synthesis, structure and materials aspects).Prog. Polym. Sci.2002,27,1473-1572.
    [140] Ozeki, T.; Yuasa, H.; Kanaya, Y. Controlled release from solid dispersion composed ofpoly(ethylene oxide)-Carbopol interpolymer complex by with various cross-linking degrees ofCarbopol. J. Controlled Release2000,63,287-295.
    [141] Lele, B. S.; Hoffman, A. S. Mucoadhesive drug carriers based on complexes of poly(acrylic acid)and PEGylated drugs having hydrolysable PEG–anhydride–drug linkages. J. Controlled Release2000,69,237-248.
    [142] Carelli, V.; Di Colo, G.; Nannipieri, E.; Poli, B.; Serafini, M. F.Poly(oxyethylene)-Poly(methacrylic acid-co-methyl methacrylate) compounds for site specific peroral delivery. Int. J. Pharm.2000,202,103-112.
    [143] Chun, M.-K.; Cho, C.-S.; Choi, H.-K. Mucoadhesive drug carrier based on interpolymer complexof poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization. J. Control.Release2002,81,327-334.
    [144] Umana, E.; Ougizawa, T.; Inoue, T. Preparation of new membranes by complex formation ofitaconic acid acrylamide copolymer with polyvinylpyrrolidone: studies on gelation mechanism bylight scattering. J. Membr. Sci.1999,157,85-96.
    [145] Sotiropoulou, M.; Bokias, G.; Staikos, G. Soluble hydrogen-bonding interpolymer complexes andpH-controlled thickening phenomena in water. Macromolecules2003,36,1349-1354.
    [146] Harada, A.; Li, J.; Kamachi, M. The molecular necklace: a rotaxane containing many threadedα-cyclodextrins. Nature1992,356,325-327.
    [147] Koopmans, C.; Ritter, H. Color change of N-isopropylacrylamide copolymer bearing Reichardtsdye as optical sensor for lower critical solution temperature and for host-guest interaction withβ-cyclodextrin. J. Am. Chem. Soc.2007,129,3502-3503.
    [148] Fujita, H.; Ooya, T.; Yui, N. Thermally induced localization of cyclodextrins in a polyrotaxaneconsisting of β-cyclodextrins and poly(ethylene glycol)-poly(propylene glycol) triblock copolymer.Macromolecules1999,32,2534-2541.
    [149] Wenz, G.; Keller, B. Threading cyclodextrin rings on polymer chains. Angew. Chem. Int. Ed.1992,31,197-199.
    [150] Sabadini, E.; Cosgrove, T. Inclusion complex formed between star-poly(ethylene glycol) andcyclodextrins. Langmuir2003,19,9680-9683.
    [151] Nostro, P. L.; Lopes, J. R.; Cardelli, C. Formation of cyclodextrin-based polypseudorotaxanes:solvent effect and kinetic study. Langmuir2001,17,4610-4615.
    [152] Jiao, H.; Goh, S. H.; Valiyaveettil, S. Inclusion complexes of poly(neopentyl glycol sebacate) withcyclodextrins. Macromolecules2001,34,8138-8142.
    [153] Ritter, H.; Tabatabai, M. Cyclodextrin in polymer synthesis: a green way to polymers. Prog. Polym.Sci.2002,27,1713-1720.
    [154] Rusa, C. C.; Bridges, C.; Ha, S. W.; Tonelli, A. E. Conformational changes induced in bombyxmori silk fibroin by cyclodextrin inclusion complexation. Macromolecules2005,38,5640-5646.
    [155] Chen, L.; Zhu, X.; Yan, D.; Chen, Y.; Chen, Q.; Yao, Y. Controlling Polymer Architecture throughHost-Guest Interactions. Angew. Chem. Int. Ed.2006,45,87-90.
    [156] Xue, J.; Jia, Z. F.; Jiang, X. L.; Wang, Y. P.; Chen, L.; Zhou, L.; He, P.; Zhu, X. Y.; Yan, D. Y.Kinetic separation of polymers with different terminals through inclusion complexation withcyclodextrin. Macromolecules2006,39,8905-8907.
    [157] Hwang, M. J.; Bae, H. S.; Kim, S. J.; Jeong, B. Polyrotaxane hexagonal microfiber.Macromolecules2004,37,8820-8822.
    [158] Chung, J. W.; Kang, T. J.; Kwak, S. Y. Supramolecular self-assembly of architecturally variantalpha-cyclodextrin inclusion complexes as building blocks of hexagonally aligned microfibrils.Macromolecule s2007,40,4225-4234.
    [159] Wang, Y. P.; Zhou, L.; Sun, G. M.; Xue, J.; Jia, Z. F.; Zhu, X. Y.; Yan, D. Y. Construction ofdifferent supramolecular polymer systems by combining the host-guest and hydrogen-bondinginteractions. J. Polym. Sci.: Polym. Phys. Ed.2008,46,1114-1120.
    [160] Bailey, F. E. Jr.; Lundberg, R. D.; Callard, R. W. Some factors affecting the molecular associationof poly(ethylene oxide) and poly(acrylic acid) in aqueous solution. J. Polym. Sci., Part A1964,2,845-851.
    [161] Zhuunuspayev, D. E.; Mun, G. A.; Hole, P.; Khutoryanskiy, V. V. Solvent effects on the formationof nanoparticles and multilayered coatings based on hydrogen-bonded interpolymer complexes ofpoly(acrylic acid) with homo-and copolymers of N-vinyl pyrrolidone. Langmuir2008,24,13742-13747.
    [162] Cameron, K. S.; Fielding, L. NMR diffusion coefficient study of steroid–cyclodextrin inclusioncomplexes. Magn. Reson. Chem.2002,40, S106-S109.
    [163] Cohen, Y.; Avram, L.; Frish, L. Diffusion NMR spectroscopy in supramolecular and combinatorialchemistry: an old parameter-new insights. Angew. Chem. Int. Ed.2005,44,520-554.
    [164] Harada, A.; Li, J.; Kamachi, M. Preparation and properties of inclusion complexes ofpoly(ethy1ene glycol) with α-cyclodextrin. Macromolecules1993,26,5698-5703.
    [165] Gidley, M. J.; Bociek, S. M. Carbon-13CP/MAS NMR studies of amylose inclusion complexes,cyclodextrins, and the amorphous phase of starch granules: relationships between glycosidiclinkage conformation and solid-state carbon-13chemical shifts. J. Am. Chem. Soc.1988,110,3820-3829.
    [166] Miyoshi, T.; Takegoshi, K.; Hikchi K. High-resolution solid state C-13nmr study of theinterpolymer interaction, morphology and chain dynamics of the poly(acrylic acid)/poly(ethyleneoxide) complex. Polymer1997,38,2315-2320.
    [167] Lu, X. Y.; Weiss, R. A. Phase behavior of blends of poly(ethylene glycol) and partially neutralizedpoly(acrylic acid). Macromolecules1995,28,3022-3029.
    [168] Ren, L. X.; He, L. H.; Sun, T. C.; Dong, X.; Chen, Y. M.; Huang, J.; Wang, C. Dual-responsivesupramolecular hydrogels from water-soluble PEG-grafted copolymers and cyclodextrin.Macromol. Biosci.2009,9,902-910.
    [169] Jiao, H.; Goh, S. H. Valiyaveettil, S. Inclusion complexes of multiarm poly(ethylene glycol) withcyclodextrins. Macromolecules2002,35,1980-1983.
    [170] Sabadini, E.; Cosgrove, T. Inclusion complex formed between star-poly(ethylene glycol) andcyclodextrins. Langmuir2003,19,9680-9683.
    [171] Yang, C.; Li, J. Thermoresponsive behavior of cationic polyrotaxane composed of multiplepentaethylenehexamine-grafted α-cyclodextrins threaded on poly(propylene oxide)-poly(ethyleneoxide)-poly(propylene oxide) triblock copolymer. J. Phys. Chem. B2009,113,682-690.
    [172] Wu, Y. L.; Li, J. Synthesis of supramolecular nanocapsules based on threading of multiplecyclodextrins over polymers on gold nanoparticles. Angew. Chem. Int. Ed.2009,48,3842-3845.
    [173] Liu, J. H.; Sondjaja, H. R.; Tam, K. C. α-Cyclodextrin-induced self-assembly of adouble-hydrophilic block copolymer in aqueous solution. Langmuir2007,23,5106-5109.
    [174] Fujita, H.; Ooya, T,; Kurisawa, M.; Mori, H.; Terano, M.; Yui, N. Thermally switchablepolyrotaxane as a model of stimuliresponsive supramolecules for nano-scale devices. Macromol.Rapid Commun.1996,17,509-515.
    [175] Ikeda, T.; Watabe, N.; Ooya, T.; Yui, N. Study on the solution properties of thermo-responsivepolyrotaxanes with different numbers of cyclic molecules. Macromol. Chem. Phys.,2001,202,1338-1344.
    [176] Ooya, T.; Yui, N. Synthesis of theophylline-polyrotaxane conjugates and their drug release viasupramolecular dissociation. J. Control. Release1999,58,251-269.
    [177] Ooya, T.; Yui, N. Multivalent interactions between biotin-polyrotaxane conjugates and streptavidinas a model of new targeting for transporters. J. Control. Release2002,80,219-228.
    [178] Tokuhisa, K.; Hamada, E.; Karinaga, R.; Shimada, N.; Takeda, Y.; Kawasaki, S.; Sakurai, K.Polyrotaxane/DNA conjugate by use of intercalation: bridge formation between DNA doublehelices. Macromolecules2006,39,9480-9485.
    [179]张磊,李文,张阿方。聚合物分子刷的合成与应用。化学进展,2006,18,939-949.
    [180] Roberts, M. J.; Harris, J. M. Attachment of degradable poly(ethylene glycol) to proteins has thepotential to increase therapeutic efficacy. J. Pharm Sci.1998,87,1440-1445.
    [181] Hallden, A.; Ohisson, B.; Wesslen, B. Poly(ethylene-graft-ethylene oxide)(PE-PEO) andpoly(ethylene-co-acrylic acid)(PEAA) as compatibilizers in blends of LDPE and polyamide-6. J.Appl. Polym. Sci.2000,28,2416.
    [182] Lin, J. J.; Chang, I. J.; Chen, C. N.; Kwan, C. C. Synthesis, characterization, and interfacialbehaviors of poly(oxyethylene)-grafted SEBS copolymers. Ind. Eng. Chem. Res.2000,39,65-71.
    [183] Olugebefola, S. C.; Park, S. Y.; Banerjee, P.; Mayers, A. M.; Santini, C. M.; Iyer, B. J. Hammond, P.T. Multiparticle effects on the interactions of complex colloidal dispersions. Langmuir2002,4,1098-1103.
    [184] Hooper, R.; Lyons, L. L.; Mapes, M. K.; Schumacher, D.; Moline, D.; West, A., R. Highlyconductive siloxane polymers. Macromolecules2001,34,931-936.
    [185] Jannasch, P. Synthesis of Novel Aggregating Comb-Shaped Polyethers for Use as PolymerElectrolytes, Macromolecule,2002,33,8604-8610.
    [186] He, L. H.; Huang, J.; Chen, Y. M.; Xu, X. J.; Liu, L. P. Inclusion interaction of highly densely PEOgrafted polymer brush and α-cyclodextrin. Macromolecules2005,38,3845-3851.
    [187] Zhang, L.; Eisenberg, A. Formation of crew-cut aggregates of various morphologies fromamphiphilic block copolymers in solution. Polym. Adv. Technol.1998,9,677.
    [188]钟玲,超支化多臂星型嵌段共聚物的RAFT合成及其自组装行为研究,[博士论文],上海,上海交通大学,2008.
    [189] Schneider, H.-J.; Hacket, F.; Rudiger, V.; Ikeda, H. NMR studies of cyclodextrins and cyclodextrincomplexes. Chem. Rev.1998,98,1755-1786.
    [190] Harada, A.; Li, J.; Kamachi, M. Formation of inclusion complexes of monodisperse oligo(ethyleneglycol)s with α-cyclodextrin, Macromolecules1994,27,4538-4543.
    [191] Wu, D. C.; Liu, Y.; Jiang, X.; He, C. B.; Goh, S. H.; Leong, K. W. Hyperbranched poly(aminoester)s with different terminal amine groups for DNA delivery. Biomacromolecules2006,7,1879-1883.
    [192] Wang, R. B.; Zhou, L. Z.; Zhou, Y. F.; Li, G. L.; Zhu, X. Y.; Gu, H. C.; Jiang, X. L.; Li, H. Q.; Wu,J. L.; He, L.; Guo, X. Q.; Zhu, B. S.; Yan, D. Y. Synthesis and gene delivery of poly(amidoamine)s with different branched architecture. Biomacromolecules2010,11,489-495.
    [193] Tang, M. X.; Redemann, C. T.; Szoka, F. C. In vitro gene delivery by degraded polyamidoaminedendrimers. Bioconjug. Chem.1996,7,703-714.
    [194] Tziveleka, L. A.; Psarra, A. M. G.; Tsiourvas, D.; Paleos, C. M. Synthesis and evaluation offunctional hyperbranched polyetherpolyols as prospected gene carriers. Int. J. Pharm.2008,356,314-324.
    [195] Brissault, B.; Kichler, A.; Leborgne, C.; Danos, O.; Cheradame, H.; Gau, J.; Auvray, L.; Guis, C.Synthesis, characterization, and gene transfer application of poly(ethylene glycol-b-ethylenimine)with high molar mass polyamine block. Biomacromolecules2006,7,2863-2870.
    [196] Lim, Y.-B.; Kim, S.-M.; Suh, H.; Park, J.-S. Biodegradable, endosome disruptive, and cationicnetwork-type polymer as a highly efficient and nontoxic gene delivery carrier. Bioconjug. Chem.2002,13,952-957.
    [197] Blacklock, J.; You, Y. Z.; Zhou, Q. H.; Mao, G. Z. Oupicky, D. Gene delivery in vitro and in vivofrom bioreducible multilayered polyelectrolyte films of plasmid DNA. Biomaterials2009,30,939-950.
    [198] Mellet, C. O.; G. Fernández, J. M. G.; Benito, J. M. Cyclodextrin-based gene delivery systems.Chem. Soc. Rev.2011,40,1586-1608.
    [199] Li, J. J.; Zhao, F.; Li, J. Supramolecular polymers based on cyclodextrins for drug and gene delivery.Adv. Biochem. Engin./Biotechnol.2011,125,207-249.
    [200] Ooya, T.; Choi, H. S.; Yamashita, A.; Yui, N.; Sugaya, Y.; Kano, A.; Maruyama, A.; Akita, H.; Ito,R.; Kogure, K.; Harashima, H. Biocleavable polyrotaxane-plasmid DNA polyplex for enhancedgene delivery. J. Am. Chem. Soc.2006,128,3852-3853.
    [201] Zhang, Y. W.; Huang, W.; Zhou, Y. F.; Yan, D. Y. A physical gel made from hyperbranchedpolymer gelator. Chem. Commun.2007,2587-2589.
    [202] Hawker, C. J.; Lee, R.; Fréchet, J. M. J. One-step synthesis of hyperbranched dendritic polyesters.J. Am. Chem. Soc.1991,113,4583-4588.
    [203] Mosmann, T. J. Rapid colorimetric assay for cellular growth and survival-application toporliferation and cytotoxicity assays. Immunol. Methods1983,65,55-63.
    [204] Prabaharan, M.; Grailer, J. J.; Pilla, S.; Steeber, D. A.; Gong, S. Amphiphilic multi-arm blockcopolymer based on hyperbranched polyester, poly(L-lactide) and poly(ethylene glycol) as a drugdelivery carrier. Macromol. Biosci.2009,9,515-524.
    [205] Stasko, N. A.; Johnson, C. B.; Schoenfisch, M. H.; Johnson, T.; Holmuhamedov, E. L. Cytotoxicityof polypropylenimine dendrimer conjugates on cultured endothelial cells. Biomacromolecules2007,8,3853-3859.
    [206] Zintchenko, A.; Philipp, A.; Dehshahri A.; Wagner, E. Simple modifications of branched PEI leadto highly efficient siRNA carriers with low toxicity. Bioconjugate Chem.2008,19,1448-1455.
    [207] Escriou, V.; Ciolina, C.; Lacroix, F.; Byk, G.; Scherman, D.; Wils, P. Cationic lipid-mediated genetransfer: effect of serum on cellular uptake and intracellular fate of lipopolyamine/DNA complexes.Biochimica et Biophysica Acta1998,1368,276-288.
    [208] Loftsson, T.; Brewster, M. E. Pharmaceutical applications of cyclodextrins.1. drug solubilizationand stabilization. J. Pharm. Sci.1996,85,1017-1025.
    [209] Irie, T.; Uekama, K. Pharmaceutical applications of cyclodextrins.3. toxicological issues andsafety evaluation. J. Pharm. Sci.1997,86,147-162.
    [210] Hashimoto, M.; Morimoto, M.; Saimoto, H.; Shigemasa, Y.; Sato, T. Lactosylated chitosan forDNA delivery into hepatocytes: the effect of lactosylation on the physicochemical properties andintracellular trafficking of pDNA/chitosan complexes. Bioconjug. Chem.2006,17,309-316.
    [211] Koh, C. G.; Kang, X. H.; Xie, Y. B.; Fei, Z. Z.; Guan, J. J.; Yu, B.; Zhang, X. L.; Lee, L. J.Delivery of polyethylenimine/DNA complexes assembled in a microfluidics device. Mol. Pharm.2009,6,1333-1342.
    [212] Albertazzi, L.; Serresi, M.; Albanese, A.; Beltram, F. Dendrimer internalization and intracellulartrafficking in living cells. Mol. Pharm.2010,7,680-688.
    [213] Wang, C. F.; Feng, M.; Deng, J. J.; Zhao, Y. F.; Zeng, X.; Hana, L.; Pan, S. R.; Wu, C. B.Poly(α-glutamic acid) combined with polycation as serum-resistant carriers for gene delivery. Int. J.Pharm.2010,398,237-245.
    [214] Yuan, Q.; Yeudall, W. A.; Yang, H. PEGylated polyamidoamine dendrimers with bis-arylhydrazone linkages for enhanced gene delivery. Biomacromolecules2010,11,1940-1947.
    [215] Onishi, H.; Machida, Y. Biodegradation and distribution of water-soluble chitosan in mice.Biomaterials1999,20,175-182.
    [216] Huang, M.; Khor, E.; Lim, L. Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles:effects of molecular weight and degree of deacetylation. Pharm. Res.2004,21,344-353.
    [217] Yang, H.; Kao, W. J. Synthesis and characterization of nanoscale dendritic RGD clusters forpotential applications in tissue engineering and drug delivery. Int. J. Nanomedicine2007,2,89-99.
    [218]张海玲;朱敦皖;董霞;刘兰霞;冷希岗。壳聚糖载基因纳米粒子的优化标记。生物医学工程与临床2008,12,9-12。
    [219] Wang, D. J.; Imae, T. Fluorescence emission from dendrimers and its pH dependence. J. Am. Chem.Soc.2004,126,13204-13205.
    [220] Lee, W. I.; Bae, Y.; Bard, A. J. Strong blue photoluminescence and ECL from OH-terminatedPAMAM dendrimers in the absence of gold nanoparticles. J. Am. Chem. Soc.2004,126,8358-8359.
    [221] Wang, D. J.;Imae, T.;Miki, M. Fluorescence emission from PAMAM and PPI dendrimers. J.Colloid and Interface Sci.2007,306,222-227.
    [222] Imae, T.; Chu, C. C. Fluorescence investigations of oxygen-doped simple aminie compared withfluorescent PAMAM dendrimer. Macromol. Rapid Commun.2009,30,89-93.
    [223] Saravanan, G.; Daigo, K.; Imae, T.; Hamakubo, T. Visual observation of avidin-biotin affinity byfluorescent G4.5poly(amidoamine) dendrimer. Colloids and Surfaces B: Biointerfaces.2011,83,58-60.
    [224] Pistolis, G.; Malliaris, A.; Paleos, C. M.; Tsiourvas, D. Study of poly(amidoamine) starburstdendrimers by fluorescence probing. Langmuir1997,13,5870-5875.
    [225] Larson, C. L.; Tucker, S. A. Intrinsic fluorescence of carboxylate-terminated polyamido aminedendrimers. Appl. Spectosc.2001,55,679-683.
    [226] Gao, C.; Yan, D. Y. Hyperbranched polymers: from synthesis to applications. Prog. Polym. Sci.2004,29,183-275.
    [227] Cao, L.; Yang, W. L.; Wang, C. C.; Fu, S. K. Synthesis and striking fluorescence properties ofhyperbranched poly(amido amine). J. Macromol. Sci. Part A: Pure and Applied Chem.2007,44,1-8.
    [228] Yang, W.; Pan, C. Y. Synthesis and fluorescent properties of biodegradable hyperbranchedpoly(amido amine)s. Macromol. Rapid Commun.2009,30,2096-2101.
    [229] Yang, W.; Pan, C. Y.; Luo, M. D.; Zhang, H. B. Fluorescent mannose-functionalizedhyperbranched poly(amido amine)s: synthesis and interaction with E. coli. Biomacromolecules2010,11,1840-1846.
    [230] You, Y. Z.; Yu, Z. Q.; Cui, M. M.; Hong, C. Y. Preparation of photoluminescent nanorings withcontrollable bioreducibility and stimuli-responsiveness. Angew. Chem. Int. Ed.2010,49,1099-1102.
    [231] Lemon, B.; Crooks, R. M. Preparation and characterization of dendrimer-encapsulated CdS. J. Am.Chem.Soc.2000,122,12886-12887.
    [232] Onoda, M.; Uchiyama, S.; Santa, T.; Imai, K. A photoinduced electron-transfer reagent forperoxyacetic acid,4-ethylthioacetylamino-7-phenylsulfony-2,1,3-benzoxadiazole, based on themethod for predicting the fluorescence quantum yields. Anal. Chem.2002,74,4089-4096.
    [233] Heller, C. A.; Henry, R. A.; McLaughlin, B. A.; Bliss, D. E. Fluorescence spectra and quantumyields: quinine, uranine,9,10-diphenylanthracene, and9,10-bis(phenylethynyl) anthracenes. J.Chem. Eng. Data.1974,19,214-219.

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