Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy

被引：47

作者：

An, Sai ^{[1
]}

Jiang, Xutao ^{[1
]}

Shi, Jiashu ^{[1
]}

He, Xi ^{[1
]}

Li, Jianfeng ^{[1
]}

Guo, Yubo ^{[1
]}

Zhang, Yu ^{[1
]}

Ma, Haojun ^{[1
]}

Lu, Yifei ^{[1
]}

Jiang, Chen ^{[1
,2
]}

机构：

[1] Fudan Univ, Sch Pharm, Dept Pharmaceut, Key Lab Smart Drug Delivery,Minist Educ, Shanghai 201203, Peoples R China

[2] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China

来源：

BIOMATERIALS | 2015年 / 53卷

基金：

中国国家自然科学基金;

关键词：

Self-assembled nanoparticle; RNAi; Tumor-homing and penetrating; iNGR; Glutathione triggered; Glioma therapy; CANCER-THERAPY; AMINOPEPTIDASE N; DRUG-DELIVERY; GENE DELIVERY; PEPTIDE; GOLD; VIVO; MICROENVIRONMENT; INTERFERENCE; VASCULATURE;

D O I：

10.1016/j.biomaterials.2015.02.084

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Existing limitations of common RNA interference (RNAi) oncotherapy severely compromised their therapeutic effects. In this study, a novel glioma-targeting RNAi system was developed. Single-component RNAi nanospheres were tactfully self-assembled in vitro, combining the carrier and cargo as a whole. An artificially synthesized polycation (pOEI) with redox-sensitive disulfides in structure condensed the RNAi nanospheres into more compacted nanoparticles. Then a novelly designed tumor-homing and penetrating cyclopeptide iNGR was further modified on the surface. iNGR modified RNAi nanoparticles demonstrated significantly enhanced accumulation in glioma site, remaining stable in circulation until the release of naked RNAi nanospheres were triggered off by the paranormal concentration of glutathione within glioma cells. Naked RNAi nanospheres were digested into abudant siRNA afterwards. Remarkable luciferase gene down-regulations have confirmed their outstanding RNAi effects. With specific design of sequences, the iNGR modified RNAi nanoparticles were supposed to be of great potential in safe and efficient glioma therapy in future. (C) 2015 Published by Elsevier Ltd.

引用

页码：330 / 340

页数：11

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