信号响应性基因载体及其应用研究

doi:10.3969/j.issn.0258-8021.2015.01.014

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摘要获得合适的基因载体是基因治疗取得成功的关键因素之一。由于病毒载体存在安全隐患问题，人们致力于非病毒载体的研究，但其递送效果仍不理想。为了提高其基因递送效率，改善其靶向性及特异性，并调控其在体内及细胞内的动态，研发具有响应机体内外各种物理、化学及生物信号功能的非病毒载体，逐渐形成了一个重要的研究方向，受到学术界与产业界的极大关注。本文从信号的性质及来源上，将非病毒基因载体分为响应外部物理信号和响应内部化学与生物信号；从响应模式上，将其分为响应单一信号和响应多种信号。系统阐述了此类载体的结构特点、作用机理，并对其研究进展和实际应用进行了综合评述。

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	王晶刘健* 许海燕*

关键词 ：信号应答, 刺激响应性, 非病毒基因载体, 药物递送系统

Abstract：The gene carrier is one of key factors for gene therapy. Although nonviral gene carriers have advantages in terms of their safety, the low transfection efficiency is still a major drawback for the research and therapeutic applications. In order to enhance the gene delivery efficiency and specific targeting ability, as well as to control their systematic and intracellular distribution, signal responsive nonviral carriers have been investigated and developed intensively, which can response to various physical, chemical, or biological signals. In this review, typical signal responsive gene carriers are introduced and classified into certain types according to the signal number and source. The latest progress of signal responsive carriers including their molecular structures, responding mechanisms, and biomedical applications are introduced in detail.

Key words： signal response stimulus responsive non viral gene carrier drug delivery systems

基金资助:国家自然科学基金（81271688);国家重大科学研究计划（2011CB933504）

引用本文:

王晶刘健* 许海燕*. 信号响应性基因载体及其应用研究[J]. 中国生物医学工程学报, 2015, 34(1): 99-108.
Wang Jing Liu Jian^#*Xu Haiyan^#*. Signal Response Gene Carriers. journal1, 2015, 34(1): 99-108.

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http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021.2015.01.014 或 http://cjbme.csbme.org/CN/Y2015/V34/I1/99

［1］Nishikawa M, Huang L. Nonviral vectors in the new millennium: delivery barriers in gene transfer ［J］. Hum Gene Ther, 2001, 12(8):861-870.
［2］Leong KW, Mao HQ, TruongLe VL, et al. DNApolycation nanospheres as nonviral gene delivery vehicles ［J］. J Control Release, 1998, 53(1-3):183-193.
［3］Jeong JH, Kim SW, Park TG. Molecular design of functional polymers for gene therapy ［J］. Prog Polym Sci, 2007, 32(11): 1239-1274.
［4］Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging ［J］. AAPS J, 2007, 9:128-147.
［5］Shenoy D, Little S, Langer R, et al. Poly (ethylene oxide)modified poly (βamino ester) nanoparticles as a pHsensitive system for tumortargeted delivery of hydrophobic drugs: part 2. In vivo distribution and tumor localization studies ［J］. Pharm Res, 2005, 22 (12): 2107-2114.
［6］Heskins M, Guillet JE. Solution properties of poly (Nisopropylacrylamide) ［J］. Sci Chem, A2: 1441-1455.
［7］Kurisawa M, Yokoyama M, Okano T. Gene expression control by temperature with thermoresponsive polymeric gene carriers ［J］. J Control Release, 2000, 69(1):127-137. 
［8］Li Wen, Zhang Afang, Chen Yong, et al. Low toxic, thermoresponsive dendrimers based on oligoethylene glycols with sharp and fully reversible phase transitions ［J］. Chem Commun (Camb), 2008, 45:5948-5950.
［9］Oupick D, Reschel T, Konák C, et al. Temperaturecontrolled behavior of selfassembly gene delivery vectors based on complexes of DNA with poly (llysine)graftpoly (Nisopropylacrylamide) ［J］. Macromolecules, 2003, 36: 6863-6872.
［10］Figueiredo M, Esenaliev R. PLGA nanoparticles for ultrasoundmediated gene delivery to solid tumors ［J］. J Drug Deliv, 2012, 2012:1-20.
［11］Chumakova OV, Liopo AV, Andreev VG, et al. Composition of PLGA and PEI/DNA nanoparticles improves ultrasoundmediated gene delivery in solid tumors in vivo ［J］. Cancer Lett, 2008, 261(2):215-225.
［12］Vandenbroucke RE, Lentacker I, Demeester J, et al. Ultrasound assisted siRNA delivery using PEGsiPlex loaded microbubbles ［J］. J Control Release, 2008, 1263):265-273.
［13］Sirsi SR, Hernandez SL, Zielinski L, et al. Polyplexmicrobubble hybrids for ultrasoundguided plasmid DNA delivery to solid tumors ［J］. J Control Release, 2012, 157(2):224-234.
［14］Nomikou N, Tiwari P, Trehan T, et al. Studies on neutral, cationic and biotinylated cationic microbubbles in enhancing ultrasoundmediated gene delivery in vitro and in vivo ［J］. Acta Biomater, 2012, 8(3):1273-1280.
［15］Scherer F, Anton M, Schillinger U, et al. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo ［J］. Gene Ther, 2002, 9(2):102-109.
［16］Liu Rui, Guo Yunlong, Odusoten G, et al. Coreshell Fe3O4 polydopamine nanoparticles serve multipurpose as drug carrier, catalyst support and carbon adsorbent ［J］. ACS Appl Mater Interfaces, 2013, 5(18):9167-9171.
［17］Giri S, Trewyn BG, Stellmaker MP, et al. Stimuliresponsive controlledrelease delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles ［J］. Angew Chem Int Ed Engl, 2005, 44(32):5038-5044.
［18］Filippousi M, Papadimitriou SA, Bikiaris DN, et al. Novel coreshell magnetic nanoparticles for Taxol encapsulation in biodegradable and biocompatible block copolymers: preparation, characterization and release properties ［J］. Int J Pharm, 2013, 448(1):221-230.
［19］Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer ［J］. Nat Rev Cancer, 2003 (3): 380-387．
［20］Delaney TF, Glatstein E. Photodynamic therapy of cancer ［J］. Comprehensive Therapy, 1988, 14(5):43-55.
［21］Monroe WT, McQuain MM, Chang MS, et al. Targeting expression with light using caged DNA ［J］. J Biol Chem, 1999, 274(30):20895-20900.
［22］Handwerger RG, Diamond SL. Capture and triggered release of nucleic acids from solid supports ［J］. Bioconjug Chem, 2007, 18(3):717-723.
［23］Deng Xiaojian, Zheng Nan, Song Ziyuan, et al. Triggerresponsive, fastdegradable poly (βamino ester) s for enhanced DNA unpackaging and reduced toxicity ［J］. Biomaterials, 2014, 35(18): 5006-5015.
［24］Yin Lichen, Tang Haoyu, Kim KH, et al. Lightresponsive helical polypeptides capable of reducing toxicity and unpacking DNA: toward nonviral gene delivery ［J］. Angew Chem Int Ed Engl, 2013, 52(35):9182-9186.
［25］Li Wenyu, Du Jianwei, Zheng Kun, et al. Multifunctional nanoparticles via hostguest interactions: a universal platform for targeted imaging and lightregulated gene delivery ［J］. Chem Commun (Camb), 2014, 50(13): 1579-1581. 
［26］Engin K, Leeper DB, Cater JR, et al. Extracellular pH distribution in human tumours ［J］. Int J Hyperthermia, 1995, 11(2):211-216. 
［27］Mellman I, Fuchs R, Helenius A. Acidification of the endocytic and exocytic pathways ［J］. Annu Rev Biochem, 1986, 55:663-700.
［28］Yatvin MB, Kreutz W, Horwitz BA, et al. pHsensitive liposomes: possible clinical implications ［J］. Science, 1980, 210(4475): 1253-1255.
［29］Cordes EH, Bull HG. Mechanism and catalysis for hydrolysis of acetals, ketals, and ortho esters ［J］. Chem Rev, 1974, 74(5): 581-603.
［30］Tseng SJ, Zeng YiFang, Deng YuFan, et al. Switchable delivery of small interfering RNA using a negatively charged pHresponsive polyethyleniminebased polyelectrolyte complex ［J］. Chem Commun (Camb), 2013, 49(26):2670-2672.
［31］Tseng Wenchi, Su Lingyu, Fang Tsueiyun. pH responsive PEGylation through metal affinity for gene delivery mediated by histidinegrafted polyethylenimine ［J］. J Biomed Mater Res B Appl Biomater, 2013, (2):375-386.
［32］Kobayashi K, Agari T, Oka M, et al. Detection of seizureassociated highfrequency oscillations above 500 Hz ［J］. Epilepsy Res, 2010, 88(2-3):139-144.
［33］Murthy N, Campbell J, Fausto N, et al. Design and synthesis of pHresponsive polymeric carriers that target uptake and enhance the intracellular delivery of oligonucleotides ［J］. J Control Release, 2003, 89(3):365-374.
［34］Du Jinzhi, Du Xiaojiao, Mao Chengqiong, et al. Tailormade dual pHsensitive polymerdoxorubicin nanoparticles for efficient anticancer drug delivery ［J］. J Am Chem Soc, 2011, 133(44): 17560-17563.
［35］Raina S, Missiakas D. Making and breaking disulfide bonds ［J］. Annu Rev Microbiol, 1997, 51:179-202.
［36］Chen Jun, Wu Chao, Oupick D. Bioreducible hyperbranched poly (amido amine) s for gene delivery ［J］. Biomacromolecules, 2009, 10(10):2921-2927.
［37］Manickam DS, Li Jing, Putt DA, et al. Effect of innate glutathione levels on activity of redoxresponsive gene delivery vectors ［J］. J Controll Release, 2010, 141: 77-84.
［38］Ping Yuan, Hu Qida, Tang Guping, et al. FGFRtargeted gene delivery mediated by supramolecular assembly between βcyclodextrincrosslinked PEI and redoxsensitive PEG ［J］. Biomaterials, 2013, 34(27):6482-6494.
［39］Azagarsamy MA, Sokkalingam P, Thayumanavan S. Enzymetriggered disassembly of dendrimerbased amphiphilic nanocontainers ［J］. J Am Chem Soc, 2009, 131(40):14184-14185.
［40］Duncan R. Designing polymer conjugates as lysosomotropic nanomedicines ［J］. Biochem Soc Trans, 2007, 35(Pt 1):56-60.
［41］Rainer H, Wiebke F, Abdul QM, et al. Compounds suited as nanocarriers for active agents and their use ［P］. European Patent Application: 12/994165, 2011-04-07.
［42］Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer—trials and tribulations ［J］. Science, 2002, 295(5564): 2387-2392.
［43］Hatakeyama H, Akita H, Kogure K, et al. Development of a novel systemic gene delivery system for cancer therapy with a tumorspecific cleavable PEGlipid ［J］. Gene Ther, 2007, 14(1):68-77.
［44］邢占文, 柯亨特, 王金锐, 等. 基于聚合物微泡的超声/荧光双模态造影剂的制备及成像研究［J］. 中华核医学与分子影像杂志, 2013, 2 (33):14-18.
［45］Wang Hongbo, Yang Jianhai, Li Yongmao, et al. Combining magnetic field/temperature dual stimuli to significantly enhance gene transfection of nonviral vectors ［J］. J Mater Chem B, 2013, 1: 43-51.
［46］Hao Ying, Zhang Mingzu, He Jinlin, et al. Magnetic DNA vector constructed from PDMAEMA polycation and PEGylated brushtype polyanion with crosslinkable shell ［J］. Langmuir, 2012, 28(15):6448-6460.
［47］Guo Baolin, Gao Qingyu. Preparation and properties of a pH/temperatureresponsive carboxymethyl chitosan/ poly (Nisopropylacrylamide) semiIPN hydrogel for oral dlivery of drugs ［J］. Carbohydr Res, 2007, 342(16): 2416-2422.
［48］Schmaljohann D. Thermoand pHresponsive polymers in drug delivery ［J］. Adv Drug Deliv Rev, 2006, 58(15):1655-1670.
［49］Dirksen A, Zuidema E, Williams RM, et al. Photoactivity and pH sensitivity of methyl orange functionalized poly(propyleneamine) dendrimers ［J］. Macromolecules, 2002, 35 (7): 2743-2747.
［50］Bulmus V, Woodward M, Lin L, et al. A new pHresponsive and glutathionereactive, membrane disruptive polymeric carrier for intracellular delivery of biomolecular dugs ［J］. J Control Release, 2003, 93(2):105-120.
［51］Chen Wei, Zhong Ping, Meng Fenghua, et al. Redox and pHresponsive degradable micelles for dually activated intracellular anticancer drug release ［J］. J Control Release, 013, 169(3):171-179.
［52］Klaikherd A, Nagamani C, Thayumanavan S. Multistimuli sensitive amphiphilic block copolymer assemblies ［J］. J Am Chem Soc, 2009, 131: 4830-4838.