文献类型：期刊文献

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

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

机构：[1]Shanghai Key Laboratory of New Drug Design,East China University of Science and Technology,Shanghai 200237,China;[2]Department of Pharmaceutics,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China;[3]Shanghai Key Laboratory of Functional Materials Chemistry,East China University of Science and Technology,Shanghai 200237,China;[4]Synthetic Biology and Biotechnology Laboratory,State Key Laboratory of Bioreactor Engineering,Shanghai Collaborative Innovation Center for Biomanufacturing Technology,East China University of Science and Technology,Shanghai 200237,China;[5]Optogenetics&Molecular Imaging Interdisciplinary Research Center,CAS Center for Excellence in Brain Science,East China University of Science and Technology,Shanghai 200237,China;[6]Interventional Cancer Institute of Chinese Integrative Medicine,Putuo Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China

年份：2020

卷号：10

期号：9

起止页码：1741

中文期刊名：Acta Pharmaceutica Sinica B

外文期刊名：药学学报（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2019_2020】；PubMed;

基金：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);National Natural Science Foundation of China(Grant No.81973700)

语种：英文

中文关键词：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 4 T1 cells via dual targeting to CD44 andαvβ3 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 lisht-induced DTA expression reduced 4 T1 cell viability and induced apoptosis.Furthermore,the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4 T1 tumor xenogratt 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.