文献类型：期刊文献

英文题名：Spatiotemporally controllable diphtheria toxin expression using a light-switchable transgene system combining multifunctional nanoparticle delivery system for targeted melanoma therapy

作者：He, Muye[1,2];Wang, Yan[2];Chen, Xianjun[3,4,5];Zhao, Yuzheng[3,4,5];Lou, Kaiyan[2];Wang, Yujie[2];Huang, Lei[2];Hou, Xinyu[2];Xu, Jiajun[2];Cai, Xiaoran[2];Cheng, Yi[2];Lan, Minbo[1];Yang, Yi[3,4,5];Gao, Feng[1,2,3]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Synthet Biol & Biotechnol Lab, 130 Mei Long Rd, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, CAS Ctr Excellence Brain Sci, Optogenet & Mol Imaging Interdisciplinary Res Ctr, 130 Mei Long Rd, Shanghai 200237, Peoples R China

年份：2020

卷号：319

起止页码：1

外文期刊名：JOURNAL OF CONTROLLED RELEASE

收录：;EI(收录号：20195207904595);WOS:【SCI-EXPANDED(收录号:WOS:000515538300001)】；

基金：This work was supported by Natural Science Foundation of Shanghai (contract No.17ZR1406600) and Science and Technology Commission of Shanghai Municipality (contract No.10DZ2220500 and No.11DZ2260600).

语种：英文

外文关键词：Light-switchable gene expression; Diphtheria toxin; Melanoma; Nanoparticle delivery system

摘要：Gene therapy with external gene insertion (e. g. a suicide gene) and expression specifically in mutated tumor cells has shown to be a promising strategy in treatment of tumors. However, current tumor gene therapy often suffered from low efficiency in gene expression and off-target effects which may cause damage to normal tissues. To address these issues, in this study, a light-switchable transgene nanoparticle delivery system loaded with a diphtheria toxin A (DTA) segment encoded gene, a suicide gene for tumor cells, was developed. The nanoparticles contained vitamin E succinate-grafted polyethyleneimine core and arginylglycylaspartic acid (RGD)-modified pegylated hyaluronic acid shell for targeted delivery of the loaded gene to tumor cells via receptor-mediated (CD44 and alpha v beta 3) endocytosis. Notably, the expression of target proteins in tumor cells could be conveniently regulated by adjusting the blue light intensity in the Light-On system. In in-vitro studies in cultured B16-F10 cells, the pG-DTA-loaded nano-micelles showed greatly improved inhibitory rate compared with the pG-DTA group. Moreover, in the tumor-bearing C57BL/6 mice model, the pG-DTA-loaded nanoparticle exhibited greatly improved efficacy and reduced systemic toxicity with significantly increased survival rate after 21 days. Significantly suppressed tumor angiogenesis was also identified in the nanoparticle-treated group likely due to the targeting ability of the RGD-modified nanoparticle. All the above results indicated that the combination of a light-switchable transgene system with a nanoparticle-based targeted delivery system have great potentials in gene therapy of malignant tumors with improved precision and efficacy.