摘要
基因疗法可用于治疗多种人类疾病如遗传性疾病、肿瘤、心血管疾病等。然而,由于缺乏高效无毒基因运送系统,基因疗法还没有在临床上得到广泛应用。近几年来,高分子非病毒基因载体因其众多的优点如低免疫反应、可运载任何尺寸的基因、外源基因整合几率低、制备简单方便等受到青睐。其中,聚甲基丙烯酸-N,N-二甲氨基乙酯(PDMAEMA)是一种常用的聚合物基因载体,高分子量的PDMAEMA(Mw>300kDa)可有效与DNA复合,在内涵体pH条件下具有强的缓冲能力,对多种细胞表现出较好的转染效率。但是,PDMAEMA不易降解,高分子量的PDMAEMA作为基因载体可能导致短期或长期的细胞毒性。此外,与其他阳离子聚合物相似,PDMAEMA/DNA复合物在血清条件下稳定性差,体内转染效率低。近年研究表明生物可降解PDMAEMA聚合物可望降低细胞毒性和／或提高转染效率。PDMAEMA与其他高分子基因载体如PEI和PAMAM相比,具有易于合成,结构和分子量可方便得到控制的优点。本论文采用可逆加成-断裂链转移(RAFT)活性自由基聚合的方法合成了一系列结构组成明确、分子量可控的新型PDMAEMA共聚物基因载体。主要包含以下四部分的工作：
1.合成了可以同时运输siRNA和疏水性抗癌药物紫杉醇进入癌细胞的生物可降解阳离子聚合物PDMAEMA-PCL-PDMAEMA胶束。该阳离子胶束的细胞毒性比25kDa PEI低,能运载GFP siRNA进入MDA-MB-435-GFP细胞,基因沉默效率最高达70%以上；而25kDa bPEI在最佳N/P比条件下基因沉默效率约为40%,20kDaPDMAEMA均聚物在最高N/P比为36/1时,仍不能抑制细胞GFP的表达。另外,对人前列腺癌细胞PC-3的体外转染实验和共聚焦显微观察都表明该阳离子聚合物胶束可以同时运输紫杉醇和VEGF siRNA进入癌细胞,能更加有效地抑制细胞的VEGF表达(基因沉默效率85%),有效结合了药物治疗和基因治疗,是一种具有应用前景的载体。
2.合成了新型还原敏感的三嵌段共聚物PDMAEMA-SS-PEG-SS-PDMAEMA作为基因载体。该三嵌段共聚物可以有效地压缩DNA,复合物粒径小于120nm；复合物的表面电位接近于中性,在0-+6mV之间,远小于PDMAEMA均聚物与DNA形成的复合物的表面电荷ca.+15mV；复合物在生理盐环境下稳定性好。动态激光光散射和凝胶电泳阻滞实验结果表明,在模拟细胞内的还原环境下,可以去PEG屏蔽,导致DNA解离。可还原降解PDMAEMA-SS-PEG-SS-PDMAEMA在血清存在下的转染效率最高时比不可还原降解PDMAEMA-PEG-PDMAEMA的转染效率高28倍,是有一种具有应用前景的基因载体。
3.合成了分子量和结构组成可控的侧链含伯胺基团的PDMAEMA共聚物作为基因载体。共聚物在N/P比为3/1时能有效压缩DNA,复合物粒径小于PDMAEMA均聚物与DNA的复合物粒径。共聚物保持了PDMAEMA均聚物的低细胞毒性。在无血清条件下的转染效率顺序为P(DMAEMA/AHMA)>P(DMAEMA/AEMA)> PDMAEMA,共聚物P(DMAEMA/AHMA)的转染效率最高时是PDMAEMA均聚物在同等条件下的24倍；共聚物在有血清存在下的转染效率与25kDa PEI相当或者更高。
4.合成了可还原降解的PDMAEMA-SS-PCL-SS-PDMAEMA阳离子聚合物胶束作为基因载体。嵌段共聚物是以含硫硫键的聚己内酯大分子RAFT试剂CPADN-SS-CL-SS-CPADN为链转移剂,通过RAFT聚合制备得到。阳离子胶束可以有效地压缩DNA,复合物表面携带正电荷,在生理盐环境条件下稳定性好。动态激光光散射和凝胶电泳阻滞实验结果表明,在模拟细胞内的还原环境下可以使DNA解离。可还原降解的阳离子聚合物胶束的细胞毒性比不可还原降解的阳离子胶束的细胞毒性要小得多,在浓度为12μg/mL时,细胞的存活率仍在80%以上,是有一种具有潜力的基因载体。
Gene therapy is one of the most promising treatments for various diseases such as cancers, cardiovascular diseases, and genetic disorders. The clinical applications of gene therapy, however, are restricted by shortage of safe, efficient gene delivery technology. In the past decade, polymer-based gene delivery systems have attracted great attention due to many advantages including improved safety, low immune responses, enabling repeated uses, and ease of production. Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) has been often studied for gene transfection.High molecular weight (Mw>300 kDa) PDMAEMA has show to display high buffer capacity at endosomal pH and mediates efficient transfection in various types of cells. However, PDMAEMA is not readily biodegradable, which may render long-term and/or acute toxicity. In addition, polyplexes of PDMAEMA expose insufficient colloidal and serum stability, which restricts their applications in vivo. In the past years, bioreducible and biodegradable PDMAEMA copolymers have been developed to achieve reduced toxicity and/or enhanced transfection activity. Furthermore, unlike other cationic polymers including PEI and PAMAM, PDMAEMA copolymers can be conveniently prepared with controlled macromolecular structures and compositions by living radical polymerization. In this paper, we adopted reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare several new types of PDMAEMA copolymers for gene delivery.
First, biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers were designed for the combinatorial delivery of siRNA and paclitaxel into cancer cells. The cationic micelles revealed lower cytotoxicity than 25 kDa branched PEI. Notably, GFP siRNA complexed with micelle achieved over 70% silencing efficiency at an N/P ratio of 36/1 which is higher than 25kDa bPEI (40% silencing efficiency). In contrast,20 kDa PDMAEMA revealed no silencing effect at an N/P ratio of 36/1.Moreover, the combinatorial delivery of VEGF siRNA and paclitaxel resulted in significantly lower VEGF expression as compared to delivery of VEGF siRNA or paclitaxel alone, reaching a high silencing efficiency of ca.85%. Confocal laser scanning microscope (CLSM) studies revealed that nile red was delivered into MDA-MB-435-GFP cells and that GFP expression was significantly inhibited. These results demonstrated that cationic biodegradable micelles are highly promising for the combinatorial delivery of siRNA and lipophilic anticancer drugs.
Second, bioreducible PDMAEMA-SS-PEG-SS-PDMAEMA triblock copolymers were designed, prepared and investigated for gene transfection. Like the non-reducible analogues, PDMAEMA-SS-PEG-SS-PDMAEMA triblock copolymers could effectively condense DNA into small particles with average diameters less than 120 nm and zeta potentials close to neutral (0-+6 mV) at and above an N/P ratio of 3/1. The resulting polyplexes showed excellent colloidal stability against 150 mM NaCl, which contrasts with polyplexes of 20 kDa PDMAEMA homopolymer. In the presence of 10 mM DTT, however, polyplexes of PDMAEMA-SS-PEG-SS-PDMAEMA were rapidly de-shielded and unpacked. Release of DNA in response to 10 mM DTT was further confirmed by gel retardation assays. Notably, in vitro transfection studies showed that reversibly shielded polyplexes afforded up to 28 times higher transfection efficacy as compared to stably shielded control under the same conditions. These results demonstrated that reversibly shielded DNA polyplexes have a great potential in achieving safe and efficient gene transfection.
Third, a versatile family of PDMAEMA copolymers containing varying amounts of primary amino side groups were synthesized and investigated for in vitro gene transfection. The copolymer compositions were well controlled by feed ratios. These PDMAEMA copolymers could effectively condense DNA at an N/P ratio of 3/1 to give small sized polyplexes, which were smaller than for PDMAMEA. The polyplexes of these copolymers revealed similar level of cytotoxicity as those of PDMAEMA homopolymer. Interestingly, the in vitro transfection in COS-7 cells in serum free medium demonstrated significantly enhanced (up to 24-fold) transfection efficiencies for PDMAEMA copolymer polyplexes as compared to PDMAEMA control, with following the order of P(DMAEMA/AHMA)> P(DMAEMA/AEMA)> PDMAMEA. It is remarkable to note that in the presence of 10% serum, P(DMAEMA/AEMA) and P(DMAEMA/AHMA) displayed comparable or better transfection activity with respect to 25kDa PEI at its optimal formulation. These results suggest that cationic methacrylate copolymers are highly promising for development of safe and efficient non-viral gene transfer agents.
Last, reduction-responsive cationic micelles based on PDMAEMA-SS-PCL-SS-PDMAEMA triblock copolymers were investigated as non-viral gene vectors. PDMAEMA-SS-PCL-PDMAEMA triblock copolymers were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of dimethylaminoethyl methacrylate using CPADN-SS-PCL-SS-CPADN as RAFT agent. Both DNA complexation assay and gel retardation assay showed that the cationic micelles could effectively complex DNA at and above N/P ratios of 3/1. These resulting polyplexes showed good colloidal stability against 150 mM NaCl, which contrasts with polyplexes of 12 kDa PDMAEMA homopolymer. Notably, the polyplexes were prone to fast aggregation in the presence of 10 mM DTT, as further confirmed by gel retardation assay. Moreover, the reducible micelles from PDMAEMA-SS-PCL-SS-PDMAEMA revealed a lower cytotoxicity than corresponding non-reducible triblock copolymers.
引文
1. Cherng JY, vandeWetering P, Talsma H, Crommelin DJA, Hennink WE. Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research 1996; 13(7): 1038-1042.
2. vandeWetering P, Cherng JY, Talsma H, Hennink WE. Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes. Journal of Controlled Release 1997; 49(1): 59-69.
3. Fonseca MJ, Storm G, Hennink WE, Gerritsen WR, Haisma HJ. Cationic polymeric gene delivery of beta-glucuronidase for doxorubicin prodrug therapy. Journal of Gene Medicine 1999;1(6):407-414.
4. vandeWetering P, Cherng JY, Talsma H, Crommelin DJA, Hennink WE. 2-(dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. Journal of Controlled Release 1998; 53(1-3):145-153.
5. Lim DW, Yeom YI, Park TG. Poly(DMAEMA-NVP)-b-PEG-galactose as gene delivery vector for hepatocytes. Bioconjugate Chemistry 2000; 11(5):688-695.
6. vandeWetering P, Schuurmans-Nieuwenbroek NME, van Steenbergen MJ, Crommelin DJA, Hennink WE. Copolymers of 2-(dimethylamino)ethyl methacrylate with ethoxytriethylene glycol methacrylate or N-vinyl-pyrrolidone as gene transfer agents. Journal of Controlled Release 2000; 64(1-3):193-203.
7. Kurisawa M, Yokoyama M, Okano T. Transfection efficiency increases by incorporating hydrophobic monomer units into polymeric gene carriers. Journal of Controlled Release 2000; 68(1):1-8.
8. Hinrichs WLJ, Schuurmans-Nieuwenbroek NME, van de Wetering P, Hennink WE. Thermosensitive polymers as carriers for DNA delivery. Journal of Controlled Release 1999; 60(2-3):249-259.
9. Liu YH, Cao XH, Luo MB, Le ZG, Xu WY. Self-assembled micellar nanoparticles of a novel star copolymer for thermo and pH dual-responsive drug release. Journal of Colloid and Interface Science 2009; 329(2):244-252.
10. Lam JKW, Ma Y, Armes SP, Lewis AL, Baldwin T, Stolnik S. Phosphorylcholine-polycation diblock copolymers as synthetic vectors for gene delivery. Journal of Controlled Release 2004; 100(2):293-312.
11. Lam JKW, Armes SP, Lewis AL, Stolnik S. Folate conjugated phosphorylcholine-based polycations for specific targeting in nucleic acids delivery. Journal of Drug Targeting 2009; 17(7):512-523.
12. Rungsardthong U, Deshpande M, Bailey L, Vamvakaki M, Armes SP, Garnett MC, et al. Copolymers of amine methacrylate with poly(ethylene glycol) as vectors for gene therapy. Journal of Controlled Release 2001; 73(2-3):359-380.
13. Deshpande MC, Garnett MC, Vamvakaki M, Bailey L, Armes SP, Stolnik S. Influence of polymer architecture on the structure of complexes formed by PEG-tertiary amine methacrylate copolymers and phosphorothioate oligonucleotide. Journal of Controlled Release 2002; 81(1-2):185-199.
14. Deshpande MC, Davies MC, Garnett MC, Williams PM, Armitage D, Bailey L, et al. The effect of poly(ethylene glycol) molecular architecture on cellular interaction and uptake of DNA complexes. Journal of Controlled Release 2004; 97(1):143-156.
15. Lin S, Du FS, Wang Y, Ji SP, Liang DH, Yu L, et al. An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems. Biomacromolecules 2008; 9(1):109-115.
16. Blessing T, Kursa M, Holzhauser R, Kircheis R, Wagner E. Different strategies for formation of PEGylated EGF-conjugated PEI/DNA complexes for targeted gene delivery. Bioconjugate Chemistry 2001; 12(4):529-537.
17. van Steenis JH, van Maarseveen EM, Verbaan FJ, Verrijk R, Crommelin DJA, Storm G, et al. Preparation and characterization of folate-targeted pEG-coated pDMAEMA-based polyplexes. Journal of Controlled Release 2003;87(1-3): 167-176.
18. Pirotton S, Muller C, Pantoustier N, Botteman F, Collinet B, Grandfils C, et al. Enhancement of trans fection efficiency through rapid and noncovalent post-PEGylation of poly(dimethylaminoethyl methacrylate)/DNA complexes. Pharmaceutical Research 2004; 21(8):1471-1479.
19. Layman JM, Ramirez SM, Green MD, Long TE. Influence of Polycation Molecular Weight on Poly(2-dimethylaminoethyl methacrylate)-Mediated DNA Delivery In Vitro. Biomacromolecules 2009; 10(5):1244-1252.
20. You YZ, Zhou QH, Manickam DS, Wan L, Mao GZ, Oupicky D. Dually responsive multiblock copolymers via reversible addition-fragmentation chain transfer polymerization:Synthesis of temperature-and redox-responsive copolymers of poly(N-isopropylacrylamide) and poly(2-(dimethylamino)ethyl methacrylate). Macromolecules 2007; 40(24):8617-8624.
21. You YZ, Manickam DS, Zhou QH, Oupicky D. Reducible poly(2-dimethyl-aminoethyl methaerylate):Synthesis, cytotoxicity, and gene delivery activity. Journal of Controlled Release 2007; 122(3):217-225.
22. Jiang X, Lok MC, Hennink WE. Degradable-Brushed pHEMA-pDMAEMA Synthesized via ATRP and Click Chemistry for Gene Delivery. Bioconjugate Chemistry 2007; 18(6):2077-2084.
23. Funhoff AM, van Nostrum CF, Janssen A, Fens M, Crommelin DJA, Hennink WE. Polymer side-chain degradation as a tool to control the destabilization of polyplexes. Pharmaceutical Research 2004; 21(1):170-176.
24. Veron L, Ganee A, Ladaviere C, Delair T. Hydrolyzable p(DMAPEMA) polymers for gene delivery. Macromolecular Bioscience 2006 Jul;6(7):540-554.
25. Dai F, Sun P, Liu Y, Liu W. Redox-cleavable star cationic PDMAEMA by arm-first approach of ATRP as a nonviral vector for gene delivery. Biomaterials 2010; 31(3):559-569.
26. Convertine AJ, Benoit DSW, Duvall CL, Hoffman AS, Stayton PS. Development of a novel endosomolytic diblock copolymer for siRNA delivery. Journal of Controlled Release 2009; 133(3):221-229.
27. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo:polyethylenimine. Proceedings of the National Academy of Sciences of the United States of America 1995 August 1,1995; 92(16):7297-7301.
28. Lee H, Jeong JH, Park TG. A new gene delivery formulation of polyethylenimine/DNA complexes coated with PEG conjugated fusogenic peptide. Journal of Controlled Release 2001; 76(1-2):183-192.
29. Shi L, Tang GP, Gao SJ, Ma YX, Liu BH, Li Y, et al. Repeated intrathecal administration of plasmid DNA complexed with polyethylene glycol-grafted polyethylenimine led to prolonged transgene expression in the spinal cord. Gene Therapy 2003; 10(14):1179-1188.
30. Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. European Journal of Cell Biology 2004; 83(3):97-111.
31. Kichler A, Chillon M, Leborgne C, Danos O, Frisch B. Intranasal gene delivery with a polyethylenimine-PEG conjugate. Journal of Controlled Release 2002; 81(3):379-388.
32. Rudolph C, Sieverling N, Schillinger U, Lesina E, Plank C, Thuemann AF, et al. Thyroid hormone (T3)-modification of polyethyleneglycol (PEG)-polyethylene-imine (PEI) graft copolymers for improved gene delivery to hepatocytes. Biomaterials 2007; 28(10):1900-1911.
33. Park MR, Han KO, Han IK, Cho MH, Nah JW, Choi YJ, et al. Degradable polyethylenimine-alt-poly(ethylene glycol) copolymers as novel gene carriers. Journal of Controlled Release 2005; 105(3):367-380.
34. Kim YH, Park JH, Lee M, Kim Y-H, Park TG, Kim SW. Polyethylenimine with acid-labile linkages as a biodegradable gene carrier. Journal of Controlled Release 2005; 103(1):209-219.
35. Gosselin MA, Guo W, Lee RJ. Efficient Gene Transfer Using Reversibly Cross-Linked Low Molecular Weight Polyethylenimine. Bioconjugate Chemistry 2001; 12(6):989-994.
36. Choi S, Lee K-D. Enhanced gene delivery using disulfide-crosslinked low molecular weight polyethylenimine with listeriolysin o-polyethylenimine disulfide conjugate. Journal of Controlled Release 2008; 131(1):70-76.
37. Peng Q, Zhong Z, Zhuo R. Disulfide Cross-Linked Polyethylenimines (PEI) Prepared via Thiolation of Low Molecular Weight PEI as Highly Efficient Gene Vectors. Bioconjugate Chemistry 2008; 19(2):499-506.
38. Marine G-N, Sara E, Francois D. Dendritic vectors for gene transfection. New Journal of Chemistry 2007; 31:1111-1127.
39. Dufes C, Uchegbu IF, Schatzlein AG. Dendrimers in gene delivery. Advanced Drug Delivery Reviews 2005; 57(15):2177-2202.
40. Omidi Y, Hollins AJ, Drayton RM, Akhtar S. Polypropylenimine dendrimer-induced gene expression changes:The effect of complexation with DNA, dendrimer generation and cell type. Journal of Drug Targeting 2005; 13(7): 431-443.
41. Kyoung KY, Kyu PI, Lin JH, B. AR, Jeong JH, Mi KE, et al. Glucosylated Polypropylenimine Dendrimer as a Novel Gene Carrier. Key Engineering Materials 2007; 342-343:457-460.
42. Ambade AV, Savariar EN, Thayumanavan S. Dendrimeric Micelles for Controlled Drug Release and Targeted Delivery. Molecular Pharmaceutics 2005; 2(4): 264-272.
43. Cakara D, Kleimann J, Borkovec M. Microscopic Protonation Equilibria of Poly(amidoamine) Dendrimers from Macroscopic Titrations. Macromolecules 2003; 36(11):4201-4207.
44. Haensler J, Szoka FC. Polyamidoamine cascade polymers mediate efficient transfection of cells in culture. Bioconjugate Chemistry 1993; 4(5):372-379.
45. Eichman JD, Bielinska AU, Kukowska-Latallo JF, Baker JR. The use of PAMAM dendrimers in the efficient transfer of genetic material into cells. Pharmaceutical Science & Technology Today 2000; 3(7):232-245.
46. Nam HY, Nam K, Hahn HJ, Kim BH, Lim HJ, Kim HJ, et al. Biodegradable PAMAM ester for enhanced transfection efficiency with low cytotoxicity. Biomaterials 2009; 30(4):665-673.
47. Rackstraw BJ, Stolnik S, Davis SS, Bignotti F, Garnett MC. Development of multicomponent DNA delivery systems based upon poly(amidoamine)-PEG co-polymers. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression 2002; 1576(3):269-286.
48. Itaka K, Yamauchi K, Harada A, Nakamura K, Kawaguchi H, Kataoka K. Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(-lysine) block copolymer as serum-tolerable polyplex system:physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials 2003; 24(24):4495-4506.
49. Park JW, Mok H, Park TG. Physical adsorption of PEG grafted and blocked poly-l-lysine copolymers on adenovirus surface for enhanced gene transduction. Journal of Controlled Release 2010; 142(2):238-244.
50. Jeong JH, Park TG. Poly(-lysine)-g-poly(-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers. Journal of Controlled Release 2002; 82(1):159-166.
51. Hashida M, Takemura S, Nishikawa M, Takakura Y. Targeted delivery of plasmid DNA complexed with galactosylated poly(-lysine). Journal of Controlled Release 1998;53(1-3):301-310.
52. Coles DJ, Yang S, Esposito A, Mitchell D, Minchin RF, Toth I. The synthesis and characterisation of a novel dendritic system for gene delivery. Tetrahedron 2007; 63(49):12207-12214.
53. Benns JM, Choi J-S, Mahato RI, Park J-S, Kim SW. pH-Sensitive Cationic Polymer Gene Delivery Vehicle:N-Ac-poly(1-histidine)-graft-poly(l-lysine) Comb Shaped Polymer. Bioconjugate Chemistry 2000; 11(5):637-645.
54. Mao S, Sun W, Kissel T. Chitosan-based formulations for delivery of DNA and siRNA. Advanced Drug Delivery Reviews 2010; 62(1):12-27.
55. Yun YH, Jiang H, Chan R, Chen W. Sustained release of PEG-g-chitosan complexed DNA from poly(lactide-co-glycolide). Journal of Biomaterials Science, Polymer Edition 2005; 16:1359-1378.
56. Yasuhiko O, Yuki E, Aya M, Masaaki M, Jun Y. Characteristics of DEAE-dextran-MMA graft copolymer as a nonviral gene carrier. Nanomedicine: Nanotechnology, Biology, and Medicine 2007; 3:181-194.
57. Cheng N, Liu W, Cao Z, Ji W, Liang D, Guo G, et al. A study of thermoresponsive poly(N-isopropylacrylamide)/polyarginine bioconjugate non-viral transgene vectors. Biomaterials 2006; 27(28):4984-4992.
58. Mishra S, Heidel JD, Webster P, Davis ME. Imidazole groups on a linear, cyclodextrin-containing polycation produce enhanced gene delivery via multiple processes. Journal of Controlled Release 2006; 116(2):179-191.
59. Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJA, Hennink WE, Storm G. Steric stabilization of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. The Journal of Gene Medicine 2004; 6(1):64-75.
60. Merdan T, Kunath K, Petersen H, Bakowsky U, Voigt KH, Kopecek J, et al. PEGylation of Poly(ethylene imine) Affects Stability of Complexes with Plasmid DNA under in Vivo Conditions in a Dose-Dependent Manner after Intravenous Injection into Mice. Bioconjugate Chemistry 2005; 16(4):785-792.
61. Lee M, Kim SW. Polyethylene Glycol-Conjugated Copolymers for Plasmid DNA Delivery. Pharmaceutical Research 2005; 22(1):1-10.
62. Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Advanced Drug Delivery Reviews 2003; 55(3): 403-419.
63. Petersen H, Fechner PM, Martin AL, Kunath K, Stolnik S, Roberts CJ, et al. Polyethylenimine-graft-Poly(ethylene glycol) Copolymers:Influence of Copolymer Block Structure on DNA Complexation and Biological Activities as Gene Delivery System. Bioconjugate Chemistry 2002; 13(4):845-854.
64. Ogris M, Walker G, Blessing T, Kircheis R, Wolschek M, Wagner E. Tumor-targeted gene therapy:strategies for the preparation of ligand-polyethylene glycol-polyethylenimine/DNA complexes. Journal of Controlled Release 2003; 91(1-2):173-181.
65. Antoine K. Gene transfer with modified polyethylenimines. The Journal of Gene Medicine 2004; 6(S1):S3-S10.
66. Benns JM, Maheshwari A, Furgeson DY, Mahato RI, Kim SW. Folate-PEG-folate-graft-polyethylenimine-based gene delivery. Journal of Drug Targeting 2001; 9(2):123-+.
67. Itaka K, Kataoka K. Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. European Journal of Pharmaceutics and Biopharmaceutics 2009; 71(3):475-483.
68. Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, et al. Toward synthetic viruses:Endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Molecular Therapy 2005; 11(3): 418-425.
69. Knorr V, Allmendinger L, Walker GF, Paintner FF, Wagner E. An Acetal-Based PEGylation Reagent for pH-Sensitive Shielding of DNA Polyplexes. Bioconjugate Chemistry 2007; 18(4):1218-1225.
70. Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, et al. PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. Journal of the American Chemical Society 2008; 130(18): 6001-6009.
71. Knorr V, Ogris M, Wagner E. An Acid Sensitive Ketal-Based Polyethylene Glycol-Oligoethylenimine Copolymer Mediates Improved Transfection Efficiency at Reduced Toxicity. Pharmaceutical Research 2008; 25(12):2937-2945.
72. Robert CC, Tomas E, Simon SB, Jon AP, Karel U, Leonard WS. Polymer-coated polyethylenimine/DNA complexes designed for triggered activation by intracellular reduction. The Journal of Gene Medicine 2004; 6(3):337-344.
73. Parker AL, Fisher KD, Oupicky D, Read ML, Nicklin SA, Baker AH, et al. Enhanced gene transfer activity of peptide-targeted gene-delivery vectors. Journal of Drug Targeting 2005; 13(1):39-51.
74. Tseng WC, Jong CM. Improved stability of polycationic vector by dextran-grafted branched polyethylenimine. Biomacromolecules 2003; 4(5):1277-1284.
75. Wen-Chi T, Chien-Hsiang T, Tsuei-Yun F. The role of dextran conjugation in transfection mediated by dextran-grafted polyethylenimine. The Journal of Gene Medicine 2004; 6(8):895-905.
76. Ito T, Iida-Tanaka N, Niidome T, Kawano T, Kubo K, Yoshikawa K, et al. Hyaluronic acid and its derivative as a multi-functional gene expression enhancer: Protection from non-specific interactions, adhesion to targeted cells, and transcriptional activation. Journal of Controlled Release 2006; 112(3):382-388.
77. Asayama S NM, Takei Y, Akaike T, Maruyama A. Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier. Bioconjugate Chem 1998; 9(4):476-481.
78. Pun SH, Bellocq NC, Liu A, Jensen G, Machemer T, Quijano E, et al. Cyclodextrin-modified polyethylenimine polymers for gene delivery. Bioconjugate chemistry 2004; 15(4):831-840.
79. Tang GP, Guo HY, Alexis F, Wang X, Zeng S, Lim TM, et al. Low molecular weight polyethylenimines linked by beta-cyclodextrin for gene transfer into the nervous system. The Journal of Gene Medicine 2006; 8(6):736-744.
80. Neu M, Sitterberg J, Bakowsky U, Kissel T. Stabilized nanocarriers for plasmids based upon cross-linked poly(ethylene imine). Biomacromolecules 2006; 7(12): 3428-3483.
81. Neu M, Germershaus O, Mao S, Voigt K-H, Behe M, Kissel T. Crosslinked nanocarriers based upon poly(ethylene imine) for systemic plasmid delivery:In vitro characterization and in vivo studies in mice. Journal of Controlled Release 2007; 118(3):370-380.
82.Lee D, Zhang W, Shirley SA, Kong X, Hellermann GR, Lockey RF, et al. Thiolated Chitosan/DNA Nanocomplexes Exhibit Enhanced and Sustained Gene Delivery Pharmaceutical Research 2007;24(1):157-167.
83. Cho KC, Kim SH, Jeong JH, Park TG. Folate receptormediated gene delivery using folate-poly(ethylene glycol)-poly(L-lysine) conjugate. Macromol Biosci 2005; 5:512-519.
84. Hwa Kim S, Hoon J, Ji, Chul Cho K, Wan Kim S, Tae Gwan P. Target-specific gene silencing by siRNA plasmid DNA complexed with folate-modified poly(ethylenimine). Journal of Controlled Release 2005; 104(1):223-232.
85. Liang B, He ML, Xiao ZP, Li Y, Chan CY, Kung HF, et al. Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery. Biochemical and Biophysical Research Communications 2008; 367(4):874-880.
86. Choi Y, Thomas T, Kotlyar A, Islam MT, Baker Jr JR. Synthesis and Functional Evaluation of DNA-Assembled Polyamidoamine Dendrimer Clusters for Cancer Cell-Specific Targeting. Chemistry & Biology 2005; 12(1):35-43.
87. Huang RQ, Qu YH, Ke WL, Zhu JH, Pei YY, Jiang C. Efficient gene delivery targeted to the brain using a transferrin-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. FASEB J 2007 April 1,2007; 21(4):1117-1125.
88. Kim WJ, Yockman JW, Lee M, Jeong JH, Kim Y-H, Kim SW. Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis. Journal of Controlled Release 2005; 106(1-2):224-234.
89. Suh W, Han SO, Kim SW. An angiogenic, endothelial-cell-targeted polymeric gene carrier. Molecular Therapy 2002; 6(5):664-672.
90. Kim TH, Park IK, Nah JW, Choi YJ, Cho CS. Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier. Biomaterials 2004; 25(17):3783-3792.
91. Chiu S-J, Ueno NT, Lee RJ. Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin? conjugated polyethylenimine. Journal of Controlled Release 2004; 97(2):357-369.
92. Jeong JH, Lee M, Kim WJ, Yockman JW, Park TG, Kim YH, et al. Anti-GAD antibody targeted non-viral gene delivery to islet beta cells. Journal of Controlled Release 2005; 107(3):562-570.
93. Ihm J-E, Han K-O, Han I-K, Ahn K-D, Han D-K, Cho C-S. High Transfection Efficiency of Poly(4-vinylimidazole) as a New Gene Carrier. Bioconjugate Chemistry 2003; 14(4):707-708.
94. Oishi M, Kataoka K, Nagasaki Y. pH-Responsive Three-Layered PEGylated Polyplex Micelle Based on a Lactosylated ABC Triblock Copolymer as a Targetable and Endosome-Disruptive Nonviral Gene Vector. Bioconjugate Chemistry 2006; 17(3):677-688.
95. Boeckle S, Fahrmeir J, Roedl W, Ogris M, Wagner E. Melittin analogs with high lytic activity at endosomal pH enhance transfection with purified targeted PEI polyplexes. Journal of Controlled Release 2006; 112(2):240-248.
96. Sabine B, Ernst W, Manfred O. C-versus N-terminally linked melittin-polyethylenimine conjugates:the site of linkage strongly influences activity of DNA polyplexes. The Journal of Gene Medicine 2005; 7(10):1335-1347.
97. Funhoff AM, van Nostrum CF, Lok MC, Kruijtzer JAW, Crommelin DJA, Hennink WE. Cationic polymethacrylates with covalently linked membrane destabilizing peptides as gene delivery vectors. Journal of Controlled Release 2005; 101(1-3):233-246.
98. Min S-H, Kim DM, Kim MN, Ge J, Lee DC, Park IY, et al. Gene delivery using a derivative of the protein transduction domain peptide, K-Antp. Biomaterials 2010; 31(7):1858-1864.
99. Niren M, Isiah C, Pat S, Allan H. pH-sensitive hemolysis by random copolymers of alkyl acrylates and acrylic acid. Macromolecular Symposia 2001; 172(1):49-56.
100. Kiang T, Bright C, Cheung CY, Stayton PS, Hoffman AS, Leong KW. Formulation of chitosan-DNA nanoparticles with poly(propyl acrylic acid) enhances gene expression. Journal of Biomaterials Science, Polymer Edition 2004; 15(11):1405-1421.
101. Dean DA, Strong DD, Zimmer WE. Nuclear entry of nonviral vectors. Gene therapy 2005; 12(11):881-890.
102. Talsma SS, Babensee JE, Murthy N, Williams IR. Development and in vitro validation of a targeted delivery vehicle for DNA vaccines. Journal of Controlled Release 2006; 112(2):271-279.
103. Choi JS, Ko KS, Park JS, Kim Y-H, Kim SW, Lee M. Dexamethasone conjugated poly(amidoamine) dendrimer as a gene carrier for efficient nuclear translocation. International Journal of Pharmaceutics 2006; 320(1-2):171-178.
104. Gabrielson NP, Pack DW. Acetylation of Polyethylenimine Enhances Gene Delivery via Weakened Polymer/DNA Interactions. Biomacromolecules 2006; 7(8):2427-2435.
105. Swami A, Aggarwal A, Pathak A, Patnaik S, Kumar P, Singh Y, et al. Imidazolyl-PEI modified nanoparticles for enhanced gene delivery. International Journal of Pharmaceutics 2007; 335(1-2):180-192.
106. Erbacher P, Roche AC, Monsigny M, Midoux P. The reduction of the positive charges of polylysine by partial gluconoylation increases the transfection efficiency of polylysine/DNA complexes. Biochimica et Biophysica Acta (BBA)-Biomembranes 1997; 1324(1):27-36.
107. Luten J, Akeroyd N, Funhoff A, Lok MC, Talsma H, Hennink WE. Methacrylamide polymers with hydrolysis-sensitive cationic side groups as degradable gene carriers. Bioconjugate Chemistry 2006; 17(4):1077-1084.
108. Zhong ZY, Song Y, Engbersen JFJ, Lok MC, Hennink WE, Feijen J. A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s. Journal of Controlled Release 2005; 109:317-329.
109. Lim Y-b, Choi YH, Park J-s. A Self-Destroying Polycationic Polymer: Biodegradable Poly(4-hydroxy4-proline ester). Journal of the American Chemical Society 1999; 121(24):5633-5639.
110. Kim T-i, Seo HJ, Choi JS, Yoon JK, Baek J-u, Kim K, et al. Synthesis of Biodegradable Cross-Linked Poly(β-amino ester) for Gene Delivery and Its Modification, Inducing Enhanced Transfection Efficiency and Stepwise Degradation. Bioconjugate Chemistry 2005; 16(5):1140-1148.
111. Kurisawa M, Yokoyama M, Okano T. Gene expression control by temperature with thermo-responsive polymeric gene carriers. Journal of Controlled Release 2000; 69(1):127-137.
112. Mao Z, Ma L, Yan J, Yan M, Gao C, Shen J. The gene transfection efficiency of thermoresponsive N,N,N-trimethyl chitosan chloride-g-poly(N-isopropyl-acrylamide) copolymer. Biomaterials 2007; 28(30):4488-4500.
113. Twaites BR, de las Heras Alarc C, Cunliffe D, Lavigne M, Pennadam S, Smith JR, et al. Thermo and pH responsive polymers as gene delivery vectors:effect of polymer architecture on DNA complexation in vitro. Journal of Controlled Release 2004; 97(3):551-566.
114. Yang J, Zhang P, Tang L, Sun P, Liu W, Sun P, et al. Temperature-tuned DNA condensation and gene transfection by PEI-g-(PMEO2MA-b-PHEMA) copolymer-based nonviral vectors. Biomaterials 2009; 31(1):144-155.
115. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. Journal of Nutrition 2004; 134(3):489-492.
116. Manickam DS, Oupicky D. Polyplex gene delivery modulated by redox potential gradients. Journal of Drug Targeting 2006 Sep;14(8):519-526.
117. Meng FH, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials 2009; 30(12):2180-2198.
118. Jere D, Arote R, Jiang HL, Kim YK, Cho MH, Cho CS. Bioreducible polymers for efficient gene and siRNA delivery. Biomed Mater 2009; 4(025020).
119. Lin C, Engbersen JFJ. The role of the disulfide group in disulfide-based polymeric gene carriers. Expert Opinion on Drug Delivery 2009; 6(4):421-439.
120. Pichon C, LeCam E, Guerin B, Coulaud D, Delain E, Midoux P. Poly[Lys-(AEDTP)]:A Cationic Polymer That Allows Dissociation of pDNA/ Cationic Polymer Complexes in a Reductive Medium and Enhances Polyfection. Bioconjugate Chemistry 2001; 13(1):76-82.
121. Zugates GT, Anderson DG, Little SR, Lawhorn IEB, Langer R. Synthesis of Poly(β-amino ester)s with Thiol-Reactive Side Chains for DNA Delivery. Journal of the American Chemical Society 2006; 128(39):12726-12734.
122. Lin C, Zhong ZY, Lok MC, Jiang XL, Hennink WE, Feijen J, et al. Novel bioreducible poly(amido amine)s for highly efficient gene delivery. Bioconjugate Chemistry 2007; 18(1):138-145.
123. Jeong JH, Christensen LV, Yockman JW, Zhong ZY, Engbersen JFJ, Kim WJ, et al. Reducible poly(amido ethylenimine) directed to enhance RNA interference. Biomaterials 2007; 28(10):1912-1917.
124. Schmitz T, Bravo-Osuna I, Vauthier C, Ponchel G, Loretz B, Bernkop-Schnuch A. Development and in vitro evaluation of a thiomer-based nanoparticulate gene delivery system. Biomaterials 2007; 28(3):524-531.
125. Cheng H, Zhu J-L, Zeng X, Jing Y, Zhang X-Z, Zhuo R-X. Targeted Gene Delivery Mediated by Folate-polyethylenimine-block-poly(ethylene glycol) with Receptor Selectivity. Bioconjugate Chemistry 2009; 20(3):481-487.
126. Lim Y-B, Han S-O, Kong H-U, Lee Y, Park J-S, Jeong B, et al. Biodegradable Polyester, Poly[a-(4-Aminobutyl)-1-Glycolic Acid], as a Non-Toxic Gene Carrier. Pharmaceutical Research 2000;17(7):811-816.
127. Lim Y-b, Kim C-h, Kim K, Kim SW, Park J-s. Development of a Safe Gene Delivery System Using Biodegradable Polymer, Poly[a-(4-aminobutyl)4-glycolic acid]. Journal of the American Chemical Society 2000; 122(27):6524-6525.
128. Lynn DM, Langer R. Degradable Poly(β-amino esters):Synthesis, Characterization, and Self-Assembly with Plasmid DNA. Journal of the American Chemical Society 2000; 122(44):10761-10768.
129. Lynn DM, Anderson DG, Putnam D, Langer R. Accelerated Discovery of Synthetic Transfection Vectors:Parallel Synthesis and Screening of a Degradable Polymer Library. Journal of the American Chemical Society 2001; 123(33): 8155-8156.
130. Daniel GA, David ML, Robert L. Semi-Automated Synthesis and Screening of a Large Library of Degradable Cationic Polymers for Gene Delivery. Angewandte Chemie 2003; 115(27):3261-3266.
131. Anderson DG, Peng W, Akinc A, Hossain N, Kohn A, Padera R, et al. A polymer library approach to suicide gene therapy for cancer. Proceedings of the National Academy of Sciences of the United States of America 2004 November 9,2004; 101(45):16028-16033.
132. Zhong Z, Song Y, Engbersen JFJ, Lok MC, Hennink WE, Feijen J. A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s. Journal of Controlled Release 2005;109(1-3):317-329.
133. Zugates GT, Tedford NC, Zumbuehl A, Jhunjhunwala S, Kang CS, Griffith LG, et al. Gene Delivery Properties of End-Modified Poly(β-amino ester)s. Bioconjugate Chemistry 2007;18(6):1887-1896.
134. Christensen LV, Chang C-W, Kim WJ, Kim SW, Zhong Z, Lin C, et al. Reducible Poly(amido ethylenimine)s Designed for Triggered Intracellular Gene Delivery. Bioconjugate Chemistry 2006; 17(5):1233-1240.
135. Lin C, Zhong Z, Lok MC, Jiang X, Hennink WE, Feijen J, et al. Novel Bioreducible Poly(amido amine)s for Highly Efficient Gene Delivery. Bioconjugate Chemistry 2006; 18(1):138-145.
136. Lu Z-Z, Wu J, Sun T-M, Ji J, Yan L-F, Wang J. Biodegradable polycation and plasmid DNA multilayer film for prolonged gene delivery to mouse osteoblasts. Biomaterials 2008; 29(6):733-741.
137. Jiang X, Dai H, Ke C-Y, Mo X, Torbenson MS, Li Z, et al. PEG-b-PPA/DNA micelles improve transgene expression in rat liver through intrabiliary infusion. Journal of Controlled Release 2007; 122(3):297-304.
138. Wang J, Zhang P-C, Lu H-F, Ma N, Wang S, Mao H-Q, et al. New polyphosphoramidate with a spermidine side chain as a gene carrier. Journal of Controlled Release 2002; 83(1):157-168.
139. Ahn C-H, Chae SY, Bae YH, Kim SW. Biodegradable poly(ethylenimine) for plasmid DNA delivery. Journal of Controlled Release 2002; 80(1-3):273-282.
140. Arote R, Kim T-H, Kim Y-K, Hwang S-K, Jiang H-L, Song H-H, et al. A biodegradable poly(ester amine) based on polycaprolactone and polyethylenimine as a gene carrier. Biomaterials 2007; 28(4):735-744.
141. Dai F, Sun P, Liu Y, Liu W. Redox-cleavable star cationic PDMAEMA by arm-first approach of ATRP as a nonviral vector for gene delivery. Biomaterials 2010; 31(3):559-569.
142. Bikram M, Ahn C-H, Chae SY, Lee M, Yockman JW, Kim SW. Biodegradable Poly(ethylene glycol)-co-poly(l-lysine)-g-histidine Multiblock Copolymers for Nonviral Gene Delivery. Macromolecules 2004; 37(5):1903-1916.
1. Dorsett Y, Tuschl T. siRNAs:Applications in functional genomics and potential as therapeutics. Nature Reviews Drug Discovery 2004; 3(4):318-329.
2. de Fougerolles A, Vornlocher HP, Maraganore J, Lieberman J. Interfering with disease:a progress report on siRNA-based therapeutics. Nature Reviews Drug Discovery 2007; 6:443-453.
3. Castanotto D, Rossi JJ. The promises and pitfalls of RNA-interference-based therapeutics. Nature 2009; 457(7228):426-433.
4. Schaffert D, Wagner E. Gene therapy progress and prospects:synthetic polymer-based systems. Gene Therapy 2008; 15(16):1131-1138.
5. Whitehead KA, Langer R, Anderson DG. Knocking down barriers:advances in siRNA delivery. Nature Reviews Drug Discovery 2009; 8(2):129-138.
6. Zhang SB, Zhao B, Jiang HM, Wang B, Ma BC. Cationic lipids and polymers mediated vectors for delivery of siRNA. Journal of Controlled Release 2007; 123: 1-10.
7. Gary DJ, Puri N, Won YY. Polymer-based siRNA delivery:Perspectives on the fundamental and phenomenological distinctions from polymer-based DNA delivery. Journal of Controlled Release 2007; 121(1-2):64-73.
8. Kim WJ, Kim SW. Efficient siRNA Delivery with Non-viral Polymeric Vehicles. Pharmaceutical Research 2009; 26(3):657-666.
9. Howard KA. Delivery of RNA interference therapeutics using polycation-based nanoparticles. Advanced Drug Delivery Reviews 2009; 61(9):710-720.
10. Jeong JH, Mok H, Oh YK, Park TG. siRNA Conjugate Delivery Systems. Bioconjugate Chemistry 2009; 20(1):5-14.
11. Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. Journal of Controlled Release 2006; 116(2): 123-129.
12. Oishi M, Nagasaki Y, Itaka K, Nishiyama N, Kataoka K. Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile ss-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells. Journal of the American Chemical Society 2005; 127(6):1624-1625.
13. Alshamsan A, Haddadi A, Incani V, Samuel J, Lavasanifar A, Uludag H. Formulation and Delivery of siRNA by Oleic Acid and Stearic Acid Modified Polyethylenimine. Molecular Pharmaceutics 2009; 6(1):121-133.
14. Liu XD, Howard KA, Dong MD, Andersen MO, Rahbek UL, Johnsen MG, et al. The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials 2007; 28(6):1280-1288.
15. Jere D, Xu CX, Arote R, Yun CH, Cho MH, Cho CS. Poly(beta-amino ester) as a carrier for si/shRNA delivery in lung cancer cells. Biomaterials 2008; 29(16): 2535-2547.
16. Jeong JH, Christensen LV, Yockman JW, Zhong ZY, Engbersen JFJ, Kim WJ, et al. Reducible poly(amido ethylenimine) directed to enhance RNA interference. Biomaterials 2007; 28(10):1912-1917.
17. Christensen LV, Chang CW, Yockman JW, Conners R, Jackson H, Zhong ZY, et al. Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery. Journal of Controlled Release 2007; 118(2):254-261.
18. Jere D, Kim JE, Arote R, Jiang HL, Kim YK, Choi YJ, et al. Akt1 silencing efficiencies in lung cancer cells by sh/si/ssiRNA transfection using a reductable polyspermine carrier. Biomaterials 2009; 30(8):1635-1647.
19. Sun TM, Du JZ, Yan LF, Mao HQ, Wang J. Self-assembled biodegradable micellar nanoparticles of amphiphilic and cationic block copolymer for siRNA delivery. Biomaterials 2008; 29(32):4348-4355.
20. Xiong XB, Uludag H, Lavasanifar A. Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery. Biomaterials 2009; 30(2):242-253.
21. Wang Y, Wang LS, Goh SH, Yang YY. Synthesis and characterization of cationic micelles self-assembled from a biodegradable copolymer for gene delivery. Biomacromolecules 2007; 8(3):1028-1037.
22. Wang Y, Gao SJ, Ye WH, Yoon HS, Yang YY. Co-delivery of drugs and DNA from cationic core-shell nanoparticles self-assembled from a biodegradable copolymer. Nature Materials 2006; 5(10):791-796.
23. Qiu LY, Bae YH. Self-assembled polyethylenimine-graft-poly(epsilon-caprolactone) micelles as potential dual carriers of genes and anticancer drugs. Biomaterials 2007; 28(28):4132-4142.
24. Zhu JL, Cheng H, Jin Y, Cheng SX, Zhang XZ, Zhuo RX. Novel polycationic micelles for drug delivery and gene transfer. Journal of Materials Chemistry 2008; 18(37):4433-4441.
25. Cherng JY, vandeWetering P, Talsma H, Crommelin DJA, Hennink WE. Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research 1996; 13(7): 1038-1042.
26. van de Wetering P, Cherng JY, Talsma H, Crommelin DJA, Hennink WE. 2-(dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. Journal of Controlled Release 1998; 53(1-3):145-153.
27. Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJA, Hennink WE, Storm G. Steric stabilization of poly(2-(dimethylamino)ethyl methacrytate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. Journal of Gene Medicine 2004; 6(1):64-75.
28. You YZ, Manickam DS, Zhou QH, Oupicky D. Reducible poly(2-dimethyl-aminoethyl methaerylate):Synthesis, cytotoxicity, and gene delivery activity. Journal of Controlled Release 2007; 122(3):217-225.
29. Convertine AJ, Benoit DSW, Duvall CL, Hoffman AS, Stayton PS. Development of a novel endosomolytic diblock copolymer for siRNA delivery. Journal of Controlled Release 2009; 133(3):221-229.
30. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Advanced Drug Delivery Reviews 2001; 47(1):113-131.
31. Savic R, Eisenberg A, Maysinger D. Block copolymer micelles as delivery vehicles of hydrophobic drugs:Micelle-cell interactions. Journal of Drug Targeting 2006; 14(6):343-355.
32. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascular-specific growth factors and blood vessel formation. Nature 2000; 407(6801):242-248.
33. Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor-growth in vivo. Nature 1993; 362(6423):841-844.
34. Azzouz M, Ralph GS, Storkebaum E, Walmsley LE, Mitrophanous KA, Kingsman SM, et al. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004; 429(6990):413-417.
35. Reich S, Fosnot J, Kuroki A, Tang WX, Yang XY, Maguire A, et al. Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model. Molecular Vision 2003; 9(31-32):210-216.
1. Anderson WF. Human gene therapy. Nature 1998; 392(6679):25-30.
2. Verma IM, Weitzman MD. Gene therapy:Twenty-first century medicine. Annual Review Of Biochemistry 2005; 74:711-738.
3. Kaiser J. Clinical research:Death prompts a review of gene therapy vector. Science 2007; 317(5838):580-580.
4. Cavazzana-Calvo M, Thrasher A, Mavilio F. The future of gene therapy. Nature 2004; 427(6977):779-781.
5. Williams DA, Baum C. Gene therapy-new challenges ahead. Science 2003; 302 (5644):400-401.
6. Ferber D. Gene therapy:Safer and virus-free? Science 2001; 294(5547): 1638-1642.
7. Li S, Huang L. Nonviral gene therapy:promises and challenges. Gene Therapy 2000; 7(1):31-34.
8. De Laporte L, Rea JC, Shea LD. Design of modular non-viral gene therapy vectors. Biomaterials 2006; 27(7):947-954.
9. Jeong JH, Kim SW, Park TG. Molecular design of functional polymers for gene therapy. Progress in Polymer Science 2007; 32(11):1239-1274.
10. Mastrobattista E, van der Aa M, Hennink WE, Crommelin DJA. Artificial viruses: a nanotechnological approach to gene delivery. Nature Reviews Drug Discovery 2006; 5(2):115-121.
11. Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chemical Reviews 2009; 109(2):259-302.
12. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 2008; 29(24-25):3477-3496.
13. Schaffert D, Wagner E. Gene therapy progress and prospects:synthetic polymer-based systems. Gene Therapy 2008; 15(16):1131-1138.
14. Verbaan FJ, Bos GW, Oussoren C, Woodle MC, Hennink WE, Storm G. A comparative study of different cationic transfection agents for in vivo gene delivery after intravenous administration. Journal of Drug Delivery Science and Technology 2004; 14(2):105-111.
15. Hunter AC. Molecular hurdles in polyfectin design and mechanistic background to polycation induced cytotoxicity. Advanced Drug Delivery Reviews 2006; 58(14): 1523-1531.
16. Verbaan FJ, Oussoren C, Snel CJ, Crommelin DJA, Hennink WE, Storm G. Steric stabilization of poly(2-(dimethylamino)ethyt methacrytate)-based polyplexes mediates prolonged circulation and tumor targeting in mice. Journal of Gene Medicine 2004; 6(1):64-75.
17. Merdan T, Kunath K, Petersen H, Bakowsky U, Voigt KH, Kopecek J, et al. PEGylation of poly(ethylene imine) affects stability of complexes with plasmid DNA under in vivo conditions in a dose-dependent manner after intravenous injection into mice. Bioconjugate Chemistry 2005; 16(4):785-792.
18. Oupicky D, Ogris M, Howard KA, Dash PR, Ulbrich K, Seymour LW. Importance of lateral and steric stabilization of polyelectrolyte gene delivery vectors for extended systemic circulation. Molecular Therapy 2002; 5(4):463-472.
19. Lee M, Kim SW. Polyethylene glycol-conjugated copolymers for plasmid DNA delivery. Pharmaceutical Research 2005; 22(1):1-10.
20. Otsuka H, Nagasaki Y, Kataoka K. PEGylated nanoparticles for biological and pharmaceutical applications. Advanced Drug Delivery Reviews 2003; 55(3): 403-419.
21. Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. European Journal of Cell Biology 2004; 83(3):97-111.
22. Petersen H, Fechner PM, Martin AL, Kunath K, Stolnik S, Roberts CJ, et al. Polyethylenimine-graft-poly(ethylene glycol) copolymers:Influence of copolymer block structure on DNA complexation and biological activities as gene delivery system. Bioconjugate Chemistry 2002;13(4):845-854.
23. Ogris M, Walker G, Blessing T, Kircheis R, Wolschek M, Wagner E. Tumor-targeted gene therapy:strategies for the preparation of ligand-polyethylene glycol-polyethylenimine/DNA complexes. Journal of Controlled Release 2003; 91(1-2):173-181.
24. Kichler A. Gene transfer with modified polyethylenimines. Journal of Gene Medicine 2004; 6:S3-S10.
25. Benns JM, Maheshwari A, Furgeson DY, Mahato RI, Kim SW. Folate-PEG-folate-graft-polyethylenimine-based gene delivery. Journal of Drug Targeting 2001; 9(2):123-+.
26. Itaka K, Kataoka K. Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. European Journal of Pharmaceutics and Biopharmaceutics 2009; 71(3):475-483.
27. Walker GF, Fella C, Pelisek J, Fahrmeir J, Boeckle S, Ogris M, et al. Toward synthetic viruses:endosomal pH-triggered deshielding of targeted polyplexes greatly enhances gene transfer in vitro and in vivo. Molecular Therapy 2005; 11(3): 418-425.
28. Knorr V, Ogris M, Wagner E. An acid sensitive ketal-based polyethylene glycol-oligoethylenimine copolymer mediates improved transfection efficiency at reduced toxicity. Pharmaceutical Research 2008; 25(12):2937-2945.
29. Knorr V, Allmendinger L, Walker GF, Paintner FF, Wagner E. An acetal-based PEGylation reagent for pH-Sensitive shielding of DNA polyplexes. Bioconjugate Chemistry 2007; 18(4):1218-1225.
30. Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, et al. PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. Journal of the American Chemical Society 2008; 130(18): 6001-6009.
31. Meng F, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials 2009; 30(12):2180-2198.
32. Sun H, Guo B, Cheng R, Meng F, Liu H, Zhong Z. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials 2009; 30(31):6358-6366.
33. Xu YM, Meng FH, Cheng R, Zhong ZY. Reduction-sensitive reversibly crosslinked biodegradable micelles for triggered release of doxorubicin. Macromolecular Bioscience 2009; 9(12):1254-1261.
34. Xu HF, Meng FH, Zhong ZY. Reversibly crosslinked temperature-responsive nano-sized polymersomes:synthesis and triggered drug release. Journal of Materials Chemistry 2009; 19(24):4183-4190.
35. Li YL, Zhu L, Liu ZZ, Cheng R, Meng FH, Cui JH, et al. Reversibly stabilized multifunctional dextran nanoparticles efficiently deliver doxorubicin into the nuclei of cancer Cells. Angewandte Chemie International Edition 2009; 48(52): 9914-9918.
36. Kim T, Seo HJ, Choi JS, Jang HS, Baek J, Kim K, et al. PAMAM-PEG-PAMAM: Novel triblock copolymer as a biocompatible and efficient gene delivery carrier. Biomacromolecules 2004; 5(6):2487-2492.
37. Zhong ZY, Feijen J, Lok MC, Hennink WE, Christensen LV, Yockman JW, et al. Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b- polyethylenimine triblock copolymers:Synthesis, characterization, and in vitro gene transfer properties. Biomacromolecules 2005;6(6):3440-3448.
38. Dubruel P, Schacht E. Vinyl polymers as non-viral gene delivery carriers:Current status and prospects. Macromolecular Bioscience 2006;6(10):789-810.
39. Xu FJ, Li HZ, Li J, Zhang ZX, Kang ET, Neoh KG. Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino) ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery. Biomaterials 2008;29(20):3023-3033.
40. Verbaan FJ, Klouwenberg PK, van Steenis JH, Snel CJ, Boerman O, Hennink WE, et al. Application of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes for gene transfer into human ovarian carcinoma cells. International Journal of Pharmaceutics 2005; 304(1-2):185-192.
41. Cherng JY, vandeWetering P, Talsma H, Crommelin DJA, Hennink WE. Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research 1996; 13(7): 1038-1042.
42. vandeWetering P, Cherng JY, Talsma H, Hennink WE. Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes. Journal of Controlled Release 1997; 49(1): 59-69.
43. You YZ, Manickam DS, Zhou QH, Oupicky D. Reducible poly(2-dimethyl-aminoethyl methaerylate):Synthesis, cytotoxicity, and gene delivery activity. Journal of Controlled Release 2007; 122(3):217-225.
44. You YZ, Zhou QH, Manickam DS, Wan L, Mao GZ, Oupicky D. Dually responsive multiblock copolymers via reversible addition-fragmentation chain transfer polymerization:Synthesis of temperature-and redox-responsive copolymers of poly(N-isopropylacrylamide) and poly(2-(dimethylamino)ethyl methacrylate). Macromolecules 2007; 40(24):8617-8624.
45. Jiang X, Lok MC, Hennink WE. Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjugate Chemistry 2007; 18:2077-2084.
46. Zhu C, Jung S, Luo S, Meng F, Zhu X, Park TG, et al. Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. Biomaterials 2010(DOI: 10.1016/j.biomaterials.2009.11.077).
47. Funhoff AM, van Nostrum CF, Janssen A, Fens M, Crommelin DJA, Hennink WE. Polymer side-chain degradation as a tool to control the destabilization of polyplexes. Pharmaceutical Research 2004; 21(1):170-176.
48. Lowe AB, McCormick CL. Reversible addition-fragmentation chain transfer (RAFT) radical polymerization and the synthesis of water-soluble (co)polymers under homogeneous conditions in organic and aqueous media. Progress in Polymer Science 2007; 32(3):283-351.
49. Wightman L, Kircheis R, Rossler V, Carotta S, Ruzicka R, Kursa M, et al. Different behavior of branched and linear polyethylenimine for gene delivery in vitro and in vivo. Journal of Gene Medicine 2001; 3(4):362-372.
1. Li S, Huang L. Nonviral gene therapy:promises and challenges. Gene Therapy 2000; 7(1):31-34.
2. De Laporte L, Rea JC, Shea LD. Design of modular non-viral gene therapy vectors. Biomaterials 2006; 27(7):947-954.
3. Jeong JH, Kim SW, Park TG. Molecular design of functional polymers for gene therapy. Progress in Polymer Science 2007; 32(11):1239-1274.
4. Mastrobattista E, van der Aa M, Hennink WE, Crommelin DJA. Artificial viruses: a nanotechnological approach to gene delivery. Nature Reviews Drug Discovery 2006;5(2):115-121.
5. Mintzer MA, Simanek EE. Nonviral vectors for gene delivery. Chemical Reviews 2009; 109(2):259-302.
6. Ruponen M, Honkakoski P, Ronkko S, Pelkonen J, Tammi M, Urtti A. Extracellular and intracellular barriers in non-viral gene delivery. Journal of Controlled Release 2003; 93(2):213-217.
7. Wong SY, Pelet JM, Putnam D. Polymer systems for gene delivery-past, present, and future. Progress in Polymer Science 2007; 32(8-9):799-837.
8. Neu M, Fischer D, Kissel T. Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. Journal of Gene Medicine 2005; 7(8):992-1009.
9. Sonawane ND, Szoka FC, Verkman AS. Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes. Journal of Biological Chemistry 2003; 278(45):44826-44831.
10. Dufe C, Uchegbu IF, Schazlein AG. Dendrimers in gene delivery. Advanced Drug Delivery Reviews 2005; 57(15):2177-2202.
11. Boussif O, Lezoualch F, Zanta MA, Mergny MD, Scherman D, Demeneix B, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in-vivo polyethylenimine. Proceedings of the National Academy of Sciences of the United States of America 1995 Aug 1; 92(16):7297-7301.
12. Cho YW, Kim JD, Park K. Polycation gene delivery systems:escape from endosomes to cytosol. Journal of Pharmacy and Pharmacology 2003; 55(6): 721-734.
13. Akinc A, Thomas M, Klibanov AM, Langer R. Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis. Journal of Gene Medicine 2005; 7(5):657-663.
14. Putnam D, Gentry CA, Pack DW, Langer R. Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proceedings of the National Academy of Sciences of the United States of America 2001; 98(3): 1200-1205.
15. Kim TH, Ihm JE, Choi YJ, Nah JW, Cho CS. Efficient gene delivery by urocanic acid-modified chitosan. Journal of Controlled Release 2003; 93(3):389-402.
16. Lin C, Zhong ZY, Lok MC, Jiang XJ, Hennink WE, Feijen J, et al. Random and block copolymers of bioreducible poly(amido amine)s with high-and low-basicity amino groups:Study of DNA condensation and buffer capacity on gene transfection. Journal of Controlled Release 2007; 123(1):67-75.
17. Green JJ, Zugates GT, Tedford NC, Huang YH, Griffith LG, Lauffenburger DA, et al. Combinatorial modification of degradable polymers enables transfection of human cells comparable to adenovirus. Adv Mater 2007; 19:2836-2842.
18. Fukushima S, Miyata K, Nishiyama N, Kanayama N, Yamasaki Y, Kataoka K. PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery. Journal of the American Chemical Society 2005; 127(9):2810-2811.
19. Bikram M, Ahn CH, Chae SY, Lee MY, Yockman JW, Kim SW. Biodegradable poly(ethylene glycol)-co-poly(L-lysine)-g-histidine multiblock copolymers for nonviral gene delivery. Macromolecules 2004; 37(5):1903-1916.
20. Ou M, Wang XL, Xu RZ, Chang CW, Bull DA, Kim SW. Novel biodegradable poly(disulfide amine)s for gene delivery with high efficiency and low cytotoxicity. Bioconjugate Chemistry 2008; 19(3):626-633.
21. Lin C, Blaauboer CJ, Timoneda MM, Lok MC, van Steenbergen M, Hennink WE, et al. Bioreducible poly(amido amine)s with oligoamine side chains:Synthesis, characterization, and structural effects on gene delivery. Journal of Controlled Release 2008; 126(2):166-174.
22. Verbaan FJ, Klouwenberg PK, van Steenis JH, Snel CJ, Boerman O, Hennink WE, et al. Application of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes for gene transfer into human ovarian carcinoma cells. International Journal of Pharmaceutics 2005; 304(1-2):185-192.
23. Cherng JY, vandeWetering P, Talsma H, Crommelin DJA, Hennink WE. Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles. Pharmaceutical Research 1996; 13(7): 1038-1042.
24. vandeWetering P, Cherng JY, Talsma H, Hennink WE. Relation between transfection efficiency and cytotoxicity of poly(2-(dimethylamino)ethyl methacrylate)/plasmid complexes. Journal of Controlled Release 1997; 49(1): 59-69.
25. van de Wetering P, Moret EE, Schuurmans-Nieuwenbroek NME, van Steenbergen MJ, Hennink WE. Structure-activity relationships of water-soluble cationic methacrylate/methacrylamide polymers for nonviral gene delivery. Bioconjugate Chemistry 1999; 10(4):589-597.
26. You YZ, Manickam DS, Zhou QH, Oupicky D. Reducible poly(2-dimethyl-aminoethyl methaerylate):Synthesis, cytotoxicity, and gene delivery activity. Journal of Controlled Release 2007; 122(3):217-225.
27. Dai F, Sun P, Liu Y, Liu W. Redox-cleavable star cationic PDMAEMA by arm-first approach of ATRP as a nonviral vector for gene delivery. Biomaterials 2010; 31(3):559-569.
28. Jiang X, Lok MC, Hennink WE. Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery. Bioconjugate Chemistry 2007; 18:2077-2084.
29. Zhu C, Jung S, Luo S, Meng F, Zhu X, Park TG, et al. Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers. Biomaterials 2010(DOI: 10.1016/j.biomaterials.2009.11.077).
30. Funhoff AM, van Nostrum CF, Janssen A, Fens M, Crommelin DJA, Hennink WE. Polymer side-chain degradation as a tool to control the destabilization of polyplexes. Pharmaceutical Research 2004; 21(1):170-176.
31. Xu FJ, Li HZ, Li J, Zhang ZX, Kang ET, Neoh KG. Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino) ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery. Biomaterials 2008;29(20):3023-3033.
32. van de Wetering P, Cherng JY, Talsma H, Crommelin DJA, Hennink WE. 2-(dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents. Journal of Controlled Release 1998; 53(1-3):145-153.
33. Dubruel P, Schacht E. Vinyl polymers as non-viral gene delivery carriers:Current status and prospects. Macromolecular Bioscience 2006; 6(10):789-810.
34. Zhong ZY, Feijen J, Lok MC, Hennink WE, Christensen LV, Yockman JW, et al. Low molecular weight linear polyethylenimine-b-poly(ethylene glycol)-b-polyethylenimine triblock copolymers:Synthesis, characterization, and in vitro gene transfer properties. Biomacromolecules 2005; 6(6):3440-3448.
35. Lowe AB, McCormick CL. Reversible addition-fragmentation chain transfer (RAFT) radical polymerization and the synthesis of water-soluble (co)polymers under homogeneous conditions in organic and aqueous media. Progress in Polymer Science 2007; 32(3):283-351.
36. Stenzel MH. RAFT polymerization:an avenue to functional polymeric micelles for drug delivery. Chemical Communications 2008(30):3486-3503.
37. Akinc A, Lynn DM, Anderson DG, Langer R. Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery. Journal of the American Chemical Society 2003; 125(18):5316-5323.
38. Zhong ZY, Song Y, Engbersen JFJ, Lok MC, Hennink WE, Feijen J. A versatile family of degradable non-viral gene carriers based on hyperbranched poly(ester amine)s. Journal of Controlled Release 2005; 109(1-3):317-329.
39. Lin C, Zhong ZY, Lok MC, Jiang XL, Hennink WE, Feijen J, et al. Novel bioreducible poly(amido amine)s for highly efficient gene delivery. Bioconjugate Chemistry 2007; 18(1):138-145.
1. Meng FH, Hennink WE, Zhong Z. Reduction-sensitive polymers and bioconjugates for biomedical applications. Biomaterials 2009; 30(12):2180-2198.
2. Jere D, Arote R, Jiang HL, Kim YK, Cho MH, Cho CS. Bioreducible polymers for efficient gene and siRNA delivery. International Conference on Multifunctional Materials and Structures; 2008 Jul 28-31; Hong Kong, PEOPLES R CHINA; 2008.
3. Lin C, Engbersen JFJ. The role of the disulfide group in disulfide-based polymeric gene carriers. Expert Opinion on Drug Delivery 2009; 6(4):421-439.
4. Piest M, Lin C, Mateos-Timoneda MA, Lok MC, Hennink WE, Feijen J, et al. Novel poly(amido amine)s with bioreducible disulfide linkages in their diamino-units: Structure effects and in vitro gene transfer properties. Journal of Controlled Release 2008; 130(1):38-45.
5. Blacklock J, Handa H, Manickam DS, Mao GZ, Mukhopadhyay A, Oupicky D. Disassembly of layer-by-layer films of plasmid DNA and reducible TAT polypeptide. Biomaterials 2007;28(1):117-124.
6. Jeong JH, Christensen LV, Yockman JW, Zhong ZY, Engbersen JFJ, Kim WJ, et al. Reducible poly(amido ethylenimine) directed to enhance RNA interference. Biomaterials 2007; 28(10):1912-1917.
7. Mok H, Park JW, Park TG. Antisense oligodeoxylutudeotide-conjugated hyaluronic Acid/Protamine nanocomplexes for intracellular gene inhibition. Bioconjugate Chemistry 2007; 18(5):1483-1489.
8. Zhang JY, Jiang X, Zhang YF, Li YT, Liu SY. Facile fabrication of reversible core cross-linked micelles possessing thermosensitive swellability. Macromolecules 2007; 40(25):9125-9132.
9. Han SC, He WD, Li J, Li LY, Sun XL, Zhang BY, et al. Reducible Polyethylenimine Hydrogels with Disulfide Crosslinkers Prepared by Michael Addition Chemistry as Drug Delivery Carriers:Synthesis, Properties, and In Vitro Release. Journal of Polymer Science Part a-Polymer Chemistry 2009; 47(16):4074-4082.
10. Sun HL, Guo BN, Cheng R, Meng FH, Liu HY, Zhong ZY. Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin. Biomaterials 2009; 30(31):6358-6366.
11. Xu YM, Meng FH, Cheng R, Zhong ZY. Reduction-Sensitive Reversibly Crosslinked Biodegradable Micelles for Triggered Release of Doxorubicin. Macromolecular Bioscience 2009; 9(12):1254-1261.
12. Xu HF, Meng FH, Zhong ZY. Reversibly crosslinked temperature-responsive nano-sized polymersomes:synthesis and triggered drug release. Journal of Materials Chemistry 2009; 19(24):4183-4190.
13. Li YL, Zhu L, Liu ZZ, Cheng R, Meng FH, Cui JH, et al. Reversibly Stabilized Multifunctional Dextran Nanoparticles Efficiently Deliver Doxorubicin into the Nuclei of Cancer Cells13. Angewandte Chemie 2009; 121(52):10098-10102.
14. Lin C, Zhong ZY, Lok MC, Jiang XJ, Hennink WE, Feijen J, et al. Random and block copolymers of bioreducible poly(amido amine)s with high-and low-basicity amino groups:Study of DNA condensation and buffer capacity on gene transfection. Journal of Controlled Release 2007; 123(1):67-75.
15. Zugates GT, Anderson DG, Little SR, Lawhorn IEB, Langer R. Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery. Journal of the American Chemical Society 2006; 128(39):12726-12734.
16. You YZ, Manickam DS, Zhou QH, Oupicky D. A versatile approach to reducible vinyl polymers via oxidation of telechelic polymers prepared by reversible addition fragmentation chain transfer polymerization. Biomacromolecules 2007; 8(6): 2038-2044.
17. Bernkop-Schnurch A, Scholler S, Biebel RG. Development of controlled drug release systems based on thiolated polymers. Journal of Controlled Release 2000; 66(1):39-48.
18. Cerritelli S, Velluto D, Hubbell JA. PEG-SS-PPS:Reduction-sensitive disulfide block copolymer vesicles for intracellular drug delivery. Biomacromolecules 2007; 8(6): 1966-1972.
19. Lowe AB, McCormick CL. Reversible addition-fragmentation chain transfer (RAFT) radical polymerization and the synthesis of water-soluble (co)polymers under homogeneous conditions in organic and aqueous media. Progress in Polymer Science 2007; 32(3):283-351.
20. Roth PJ, Kessler D, Zentel R, Theato P. Versatile omega-End Group Functionalization of RAFT Polymers Using Functional Methane Thiosulfonates. Journal of Polymer Science Part a-Polymer Chemistry 2009; 47(12):3118-3130.
21. Moad G, Chong YK, Postma A, Rizzardo E, Thang SH. Advances in RAFT polymerization:the synthesis of polymers with defined end-groups. IUPAC World Polymer Congress; 2004 Jul 04-09; Paris, FRANCE; 2004. p.8458-8468.
22. Schilli CM, Muller AHE, Rizzardo E, Thang SH, Chong YK. RAFT polymers:Novel precursors for polymer-protein conjugates. In:Matyjaszewski K, editor.224th National Meeting of the American-Chemical-Society; 2002 Aug 17-22; Boston, Massachusetts; 2002. p.603-618.
23. Deng ZC, Ahmed M, Narain R. Novel Well-Defined Glycopolymers Synthesized via the Reversible Addition Fragmentation Chain Transfer Process in Aqueous Media. Journal of Polymer Science Part a-Polymer Chemistry 2009; 47(2):614-627.
24. Vazquez-Dorbatt V, Maynard HD. Biotinylated glycopolymers synthesized by atom transfer radical polymerization. Biomacromolecules 2006; 7(8):2297-2302.
25. Liu JQ, Liu HY, Jia ZF, Bulmus V, Davis TP. An approach to biodegradable star polymeric architectures using disulfide coupling. Chemical Communications 2008(48):6582-6584.