文献类型：期刊文献

英文题名：A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

作者：Hou, Xinyu[1,2];Shou, Chenting[2];He, Muye[2];Xu, Jiajun[2];Cheng, Yi[2];Yuan, Zeting[2,6];Lan, Minbo[3];Zhao, Yuzheng[3,4,5];Yang, Yi[3,4,5];Chen, Xianjun[3,4,5];Gao, Feng[1,2,3]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, 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 Funct Mat Chem, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg Technol, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Optogenet & Mol Imaging Interdisciplinary Res Ctr, CAS Ctr Excellence Brain Sci, Shanghai 200237, Peoples R China;[6]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China

年份：2020

卷号：10

期号：9

起止页码：1741

外文期刊名：ACTA PHARMACEUTICA SINICA B

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000577456900013)】；

基金：This work was supportedby Shanghai Municipal Natural Science Foundation (No. 17ZR1406600, China), Science and Technology Commission of Shanghai Municipality (No.10DZ2220500, China), The Shanghai Committee of Science and Technology (Grant No. 11DZ2260600, China) and National Natural Science Foundation of China (Grant No.81973700).

语种：英文

外文关键词：Light-switchable gene expression system; Nanoparticle drug delivery system; Microenvironment-responsive; Diphtheria toxin; Breast cancer

摘要：A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light, and have great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system (NDDS) to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A (DTA) fragment-encoded plasmids to tumor sites. The expression of DTA was induced by exposure to blue light. Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond, and PEGylated hyaluronic acid modified with RGD peptide, accumulated in tumor tissues and were actively internalized into 4T1 cells via dual targeting to CD44 and alpha(v)beta(3) receptors. The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure. In vitro studies showed that light-induced DTA expression reduced 4T1 cell viability and induced apoptosis. Furthermore, the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4T1 tumor xenograft model, which resulted in excellent antitumor effects, reduced tumor angiogenesis, and no systemic toxicity. The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.