用于基因传递的智能响应性高分子研究进展
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摘要
智能响应性高分子由于具有优异的环境响应性、多样的功能性、良好的生物可降解性和生物相容性而在生物医用领域备受瞩目.基于特定功能的智能响应性高分子基因载体可以克服基因运载中的障碍,降低对正常组织和细胞的毒副作用,提升靶细胞的基因转染效率.此外,大部分智能响应性高分子能有效结合多种治疗方式以实现更有效的治疗效果.本文综述了近年来智能响应性高分子在基因运载及相关生物医用领域的研究进展,对相关智能响应性高分子的设计及特点进行了介绍,并进一步对其在基因运载及相关生物医用领域的应用前景进行了展望.
Gene therapy is a remarkable technique which regulates specific gene expression in targeted cells to treat acquired and inherited diseases via exogenous nucleic acids. However, naked genes could hardly be utilized directly due to their large size, low stability in circulation and poor cellular uptake. Therefore, suitable gene vector plays a crucial role in gene therapy. Though a mass of gene delivery systems have been developed and shown extraordinary potential to treat gene-related diseases, the clinical applications of gene therapy are still limited by various biological barriers. These barriers include DNA packaging, bloodstream clearing, non-specific cellular uptake, cytomembrane obstructing, endosomal escape, DNA release and potential toxicity to normal tissues, etc.In order to overcome these barriers, the gene vectors should satisfy numerous requirements, including effective gene packaging, prolonging the circulation time in bloodstream, excellent targeting ability, the endosomal escape capability, reduced vector-induced toxicity and the capacity of stimuli-responsive gene unpacking, etc. Intelligent responsive polymers have attracted increasing research attentions in gene delivery applications due to their excellent responsiveness, superadditive versatility, prominent biodegradability and superb biocompatibility, etc.Thus, utilizing the intelligent responsive polymers with special functions could overcome a series of barriers in gene delivery. In addition, most intelligent responsive polymers can creatively combine multiple treatments for tumor therapy to achieve more effective therapeutic effects. This review highlights the designs, characteristics as well as biomedical applications of intelligent responsive polymers in gene delivery field in recent years. The types of response in intelligent responsive polymers include pH response, reduction response, enzyme response, light response and multiple response, etc. The research trends and prospects of these polymers are also discussed. In order to push forward the studies of intelligent responsive polymers in gene delivery field and to develop novel gene vectors, more research attention should be paid to responsive polymers with proper chemical properties,suitable physical properties, desired architectures and appropriate functions.
Gene therapy is a remarkable technique which regulates specific gene expression in targeted cells to treat acquired and inherited diseases via exogenous nucleic acids. However, naked genes could hardly be utilized directly due to their large size, low stability in circulation and poor cellular uptake. Therefore, suitable gene vector plays a crucial role in gene therapy. Though a mass of gene delivery systems have been developed and shown extraordinary potential to treat gene-related diseases, the clinical applications of gene therapy are still limited by various biological barriers. These barriers include DNA packaging, bloodstream clearing, non-specific cellular uptake, cytomembrane obstructing, endosomal escape, DNA release and potential toxicity to normal tissues, etc.In order to overcome these barriers, the gene vectors should satisfy numerous requirements, including effective gene packaging, prolonging the circulation time in bloodstream, excellent targeting ability, the endosomal escape capability, reduced vector-induced toxicity and the capacity of stimuli-responsive gene unpacking, etc. Intelligent responsive polymers have attracted increasing research attentions in gene delivery applications due to their excellent responsiveness, superadditive versatility, prominent biodegradability and superb biocompatibility, etc.Thus, utilizing the intelligent responsive polymers with special functions could overcome a series of barriers in gene delivery. In addition, most intelligent responsive polymers can creatively combine multiple treatments for tumor therapy to achieve more effective therapeutic effects. This review highlights the designs, characteristics as well as biomedical applications of intelligent responsive polymers in gene delivery field in recent years. The types of response in intelligent responsive polymers include pH response, reduction response, enzyme response, light response and multiple response, etc. The research trends and prospects of these polymers are also discussed. In order to push forward the studies of intelligent responsive polymers in gene delivery field and to develop novel gene vectors, more research attention should be paid to responsive polymers with proper chemical properties,suitable physical properties, desired architectures and appropriate functions.
引文
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71Pahle J,Walther W.Expert Opin Biol Th,2016,16:443-461
72Meyer R A,Sunshine J C,Green J J.Trends Biotechnol,2015,33:514-524
73Carmona-Ribeiro A M.J Liposome Res,2007,17:165-172
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2Chen J,Guan X W,Hu Y Y,Tian H Y,Chen X S.Topics Curr Chem,2017,375:32
3Marzbali M Y,Khosroushahi A Y.Cancer Chemother Pharmacol,2017,79:637-649
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35 Guan X W,Li Y H,Jiao Z X,Lin L,Chen J,Guo Z P,Tian H Y,Chen X S.ACS Appl Mater Interfaces,2015,7:3207-3215
36 Chen J J,Ding J X,Zhang Y,Xiao C S,Zhuang X L,Chen X S.Polym Chem,2015,6:397-405
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39 Chen S,Rong L,Jia H Z,Qin S Y,Zhuo R X,Zhang X Z.Biomater Sci,2015,3:753-761
40 Sun H,Meng F,Cheng R,Deng C,Zhong Z.Expert Opin Drug Deliv,2013,10:1109-1122
41 Meng F,Hennink W E,Zhong Z.Biomaterials,2009,30:2180-2198
42 Yang J,Yi W J,Sun Y X,Gong Y H,Wang H Y,Zhuo R X,Zhang X Z.Adv Healthc Mater,2013,2:481-489
43 He Y Y,Nie Y,Cheng G,Xie L,Shen Y Q,Gu Z W.Adv Mater,2014,26:1534-1540
44 He Y Y,Cheng G,Xie L,Nie Y,He B,Gu Z W.Biomaterials,2013,34:1235-1245
45 Zhu J Y,Wan S S,Zheng D W,Lei Q,Zhuo R X,Feng J,Zhang X Z.ACS Appl Mater Inter,2017,9:255-265
46 Lei Q,Jia H Z,Chen W H,Rong L,Chen S,Luo G F,Qiu W X,Zhang X Z.ACS Biomater Sci Eng,2015,1:1151-1162
47 Such G K,Yan Y,Johnston A P R,Gunawan S T,Caruso F.Adv Mater,2015,27:2278-2297
48 Gu L,Mooney D J.Nat Rev Cancer,2016,16:56-66
49 Song S J,Lee S,Choi J S.Eur J Pharm Sci,2016,91:20-30
50 Liu T W,Chen J,Burgess L,Wilson B C,Zheng G,Zhan L X,Liu W K,Ha B Y.J Phys Chem B,2015,119:44-53
51 Han K,Lei Q,Jia H Z,Wang S B,Yin W N,Chen W H,Cheng S X,Zhang X Z.Adv Funct Mater,2015,25:1248-1257
52 Zhu L,Kate P,Torchilin V P.ACS Nano,2012,6:3491-3498
53 Chien M P,Carlini A S,Hu D H,Barback C V,Rush A M,Hall D J,Orr G,Gianneschi N C.J Am Chem Soc,2013,135:18710-18713
54 Li S Y,Liu L H,Rong L,Qiu W X,Jia H Z,Li B,Li F,Zhang X Z.Adv Funct Mater,2015,25:7317-7326
55 Chen S,Lei Q,Qin W X,Liu L H,Zheng D W,Fan J X,Rong L,Sun Y X,Zhang X Z.Biomaterials,2017,117:92-104
56 Chen W H,Luo G F,Lei Q,Hong S,Qiu W X,Liu L H,Cheng S X,Zhang X Z.ACS Nano,2017,11:1419-1431
57 Qiu W X,Liu L H,Li S Y,Lei Q,Luo G F,Zhang X Z.Small,2017,13:1603956
58 Wang Y,Wang K Y,Zhang R,Liu X G,Yan X Y,Wang J X,Wagner E,Huang R Q.ACS Nano,2014,8:7870-7879
59 Xiao W,Chen W H,Xu X D,Li C,Zhang J,Zhuo R X,Zhang X Z.Adv Mater,2011,23:3526-3530
60 Chien Y H,Chou Y L,Wang S W,Hung S T,Liau M C,Chao Y J,Su C H,Yeh C S.ACS Nano,2013,7:8516-8528
61 Liu J,Bu W,Pan L,Shi J.Angew Chem Int Ed,2013,52:4375-4379
62 Vankayala R,Kuo C L,Nuthalapati K,Chiang C S,Hwang K C.Adv Funct Mater,2015,25:5934-5945
63 Chen W H,Luo G F,Qiu W X,Lei Q,Liu L H,Wang S B,Zhang X Z.Biomaterials,2017,117:54-65
64 Lei Q,Hu J J,Rong L,Cheng H,Sun Y X,Zhang X Z.Molecules,2016,21:1103
65 Chen S,Rong L,Lei Q,Cao P X,Qin S Y,Zheng D W,Jia H Z,Zhu J Y,Cheng S X,Zhuo R X,Zhang X Z.Biomaterials,2016,77:149-163
66 Han K,Lei Q,Jia H Z,Wang S B,Yin W N,Chen W H,Cheng S X,Zhang X Z.Adv Funct Mater,2015,25:1248-1257
67 Chen S,Lei Q,Li S Y,Qin S Y,Jia H Z,Cheng Y J,Zhang X Z.Biomaterials,2016,92:25-35
68 Zhang J,Yuan Z F,Wang Y,Chen W H,Luo G F,Cheng S X,Zhuo R X,Zhang X Z.J Am Chem Soc,2013,135:5068-5073
69 Keles E,Song Y,Du D,Dong W J,Lin Y.Biomater Sci,2016,4:1291-1309
70 Luo G F,Chen W H,Lei Q,Qiu W X,Liu Y X,Cheng Y J,Zhang X Z.Adv Funct Mater,2016,26:4339-4350
71Pahle J,Walther W.Expert Opin Biol Th,2016,16:443-461
72Meyer R A,Sunshine J C,Green J J.Trends Biotechnol,2015,33:514-524
73Carmona-Ribeiro A M.J Liposome Res,2007,17:165-172
74Peppas N A.Adv Drug Deliv Rev,2004,56:1529-1531
75Hu C M J,Zhang L,Aryal S,Cheung C,Fang R H,Zhang L F.Proc Natl Acad Sci USA,2011,108:10980-10985
76Gao W,Zhang L.AICh E J,2015,61:738-746
77Rao L,Bu L L,Xu J H,Cai B,Yu G T,Yu X L,He Z B,Huang Q Q,Li A,Guo S S,Zhang W F,Liu W,Sun Z J,Wang H,Wang T H,Zhao X Z.Small,2015,11:6225-6236
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