用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

王欢; 马志强; 杨峰

doi:10.3969/j.issn.1006-0111.2015.06.005

用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

doi: 10.3969/j.issn.1006-0111.2015.06.005

1.
福建中医药大学药学院, 福建福州 350122
2.
第二军医大学药学院无机化学教研室, 上海 200433

Current status of non-viral siRNA vectors for therapy of cancers

1.
School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
2.
Department of Inorganic Chemistry, School of Pharmacy, Second Militatry University, Shanghai 200433, China

摘要: 近年来,小分子干扰RNA(siRNA)作为RNA干扰 (RNAi) 技术的效应分子,已被广泛用于恶性肿瘤的基因治疗领域。欲获得理想的治疗效果,其关键因素是寻找一种安全、高效、稳定、可控的基因载体。非病毒载体具有低毒、低免疫原性、制备简单、目的基因容量大、外源基因随机整合率低且携带基因大小类型不受限制等突出优势,已经成为目前siRNA载体的研究热点。在以往学者的研究基础上,从药剂学的角度,笔者对这些载体在siRNA传递系统中的研究现况做回顾性总结。
- RNA干扰 /
- 小分子干扰RNA /
- 肿瘤 /
- 基因治疗 /
- 非病毒载体
Abstract: In the recent years, siRNA has been widely used as effector molecule in the field of gene therapy for cancer. In order to achieve ideal treatment effect, the key factor is to find safe, efficient, stable and controllable gene vectors. The commonly used vectors include viral and non-viral vectors. The non-viral gene vector has superiority of low toxicity, bare immunogenicity, simple to manufacture and high capacity which have been taken as the highlight of the research of carrier of gene drugs. Based on the study of the previous researchers, this study reviewed the prevalence study of the former carriers in the delivery system of siRNA from the point of pharmaceutics.
- RNAi /
- siRNA /
- tumor /
- gene therapy /
- non-viral vector

[1]	David S, Pitard B, Benoit JP, et al. Non-viral nanosystems for systemic siRNA delivery[J].Pharmacol Res, 2010,62(2): 100-114.
[2]	Tiemann K, Rossi JJ. RNAi-based therapeutics-current status, challenges and prospects[J].EMBO Mol Med, 2009, 1(3): 142-151.
[3]	Liu W, Chen JM. Progress in studies of the structure-activity relationship of cationic lipid-mediated gene delivery[J].Chin J New Drug, 2011,20( 20): 1975-1980.
[4]	Yang ST, Zaitseva E, Chernomordik LV, et al. Cell-penetrating peptide induces leaky fusion of liposomes containing late endosome-specific anionic lipid[J].Biophys J,2010, 99(8): 2525-2533.
[5]	Han SE, Kang H, Shim GY, et al. Novel cationic cholesterol derivative-based liposomes for serum-enhanced delivery of siRNA[J].Int J Pharm, 2008,353(1-2): 260-269.
[6]	Maslov MA, Kabilova TO, Petukhov IA, et al. Novel cholesterol spermine conjugates provide efficient cellular delivery of plasmid DNA and small interfering RNA[J].J Control Release, 2012, 160(2): 182-193
[7]	Kim J, Kim SW, W Kim WJ. PEI-g-PEG-RGD/small interference RNA polyplex-mediated silencing of vascular endothelial growth factor receptor and its potential as an anti-angiogenic tumor therapeutic strategy[J].Oligonucleotides, 2011,21(2): 101-107.
[8]	Malek A, Czubayko F, Aigner A. PEG grafting of polyethylenimine (PEI) exerts different effects on DNA transfection and siRNA-induced gene targeting efficacy[J].J Drug Target, 2008, 16(2): 124-139.
[9]	Xia W, Wang P, Lin C, et al. Bioreducible polyethylenimine-delivered siRNA targeting human telomerase reverse transcriptase inhibits HepG2 cell growth in vitro and in vivo[J].J Control Release, 2012, 157(3): 427-436.
[10]	Yu T, Liu X. Bolcato-Bellemin AL,et al. An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo[J].Angew Chem Int Ed Engl, 2012,51(34): 8478-8484.
[11]	Biswas S, Deshpande PP, Navarro GS, et al. Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery[J].Biomaterials, 2013, 34(4): 1289-12301.
[12]	Perez AP, Mundina-Weilenmann C, Romero EL, et al. Increased brain radioactivity by intranasalP-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels[J].Int J Nanomedicine, 2012, 7: 1373-1385.
[13]	Liu P, Yu H, Sun Y, et al. A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery[J].Biomaterials, 2012, 33(17): 4403-4412.
[14]	Ambardekar VV, Wakaskar RR, Sharma B, et al. The efficacy of nuclease-resistant Chol-siRNA in primary breast tumors following complexation with PLL-PEG(5K)[J].Biomaterials, 2013.4839-4848.
[15]	Christie RJ, Matsumoto Y, Miyata K, et al. Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection[J].ACS Nano, 2012, 6(6): 5174-5189.
[16]	Mumper RJ, Wang J, Claspel JM, et al. Novel polymeric condensing carriers for gene delivery[J].Symp Controlled Rel,1995, 22:178.
[17]	Zhou SM, Kong FQ, Sun B, et al. Phosphorylatable short peptide conjugated low molecular weight chitosan for efficient siRNA delivery and target gene silencing[J].Chin J Biochem Molecul Biol, 2011, 27(10): 980-986.
[18]	Pezzoli D, Olimpieri F, Malloggi C, et al. Chitosan-graft-branched polyethylenimine copolymers: influence of degree of grafting on transfection behavior[J].PLoS One, 2012, 7(4): e34711.
[19]	Davis ME. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic[J].Mol Pharm, 2009. 6(3): 659-668.
[20]	Hu T.N, Wang QW, Jin X, et al. Anticancer effect of triptolide-polyethylenimine-cyclodextrin in vitro[J].J Zhejiang Univ (Med Sci), 2012, 41(6): 610-619.
[21]	Boe SL, Longva AS, Hovig E. Cyclodextrin-containing polymer delivery system for light-directed siRNA gene silencing[J].Oligonucleotides, 2010, 20(4): 175-182.
[22]	Fang B, Jiang L, Zhang M,et al. A novel cell-penetrating peptide TAT-A1 delivers siRNA into tumor cells selectively[J].Biochimie, 2013, 95(2): 251-257.
[23]	Choi YS, Lee JY, Suh JS, et al. The systemic delivery of siRNAs by a cell penetrating peptide, low molecular weight protamine[J].Biomaterials, 2010, 31(6): 1429-1443.
[24]	Alberici L, Roth L, Sugahara KN, et al. De novo design of a tumor-penetrating peptide[J].Cancer Res, 2013, 73(2): 804-812.
[25]	Lin D, Cheng Q, Jiang Q, et al. Intracellular cleavable poly(2-dimethylaminoethyl methacrylate) functionalized mesoporous silica nanoparticles for efficient siRNA delivery in vitro and in vivo[J].Nanoscale, 2013.5, 4291-4301.
[26]	Li X, Chen Y, Wang M, et al. A mesoporous silica nanoparticle-PEI-fusogenic peptide system for siRNA delivery in cancer therapy[J].Biomaterials, 2013, 34(4): 1391-1401.

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用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

doi: 10.3969/j.issn.1006-0111.2015.06.005

Current status of non-viral siRNA vectors for therapy of cancers

计量

用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

doi: 10.3969/j.issn.1006-0111.2015.06.005

1. 福建中医药大学药学院, 福建福州 350122

2. 第二军医大学药学院无机化学教研室, 上海 200433

English Abstract

Current status of non-viral siRNA vectors for therapy of cancers

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

2. Department of Inorganic Chemistry, School of Pharmacy, Second Militatry University, Shanghai 200433, China

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用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

doi: 10.3969/j.issn.1006-0111.2015.06.005

Current status of non-viral siRNA vectors for therapy of cancers

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用于肿瘤治疗的小分子干扰RNA非病毒载体研究进展

doi: 10.3969/j.issn.1006-0111.2015.06.005

1. 福建中医药大学药学院, 福建 福州 350122 2. 第二军医大学药学院无机化学教研室, 上海 200433

English Abstract

Current status of non-viral siRNA vectors for therapy of cancers

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China 2. Department of Inorganic Chemistry, School of Pharmacy, Second Militatry University, Shanghai 200433, China

全文HTML

目录

1. 福建中医药大学药学院, 福建福州 350122

2. 第二军医大学药学院无机化学教研室, 上海 200433

1. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

2. Department of Inorganic Chemistry, School of Pharmacy, Second Militatry University, Shanghai 200433, China