文献类型：期刊文献

英文题名：Light-switchable diphtherin transgene system combined with losartan for triple negtative breast cancer therapy based on nano drug delivery system

作者：Cheng, Yi[1,2,3];Sun, Rui[1];He, Muye[1];Zhang, Miao[1];Hou, Xinyu[1];Sun, Yuji[1];Wang, Jie[1];Xu, Jiajun[1];He, Hai[1];Wang, Hongtao[1];Lan, Minbo[2];Zhao, Yuzheng[1,3,4,5,6];Yang, Yi[1,4,6];Chen, Xianjun[1,4,6,7,8];Gao, Feng[1,2,3,4,7,8]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]Chinese Acad Med Sci, Res Unit New Tech Livecell Metab Imaging, Beijing, Peoples R China;[6]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[7]East China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, 130 Meilong Rd, Shanghai 200237, Peoples R China;[8]East China Univ Sci & Technol, Sch Pharm, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2022

卷号：618

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000788847200001)】；

基金：Development Program of China (contract No.2019YFA0904800), National Nature Science Foundation of China (32030065, 31722033, 92049304 to Y.Z.), Shanghai Sailing Program (contract No.21YF1410300), Science and Technology Commission of Shanghai Municipality (contract No.10DZ2220500) and the Shanghai Committee of Science and Technology (grant No.11DZ2260600). Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education commission, grant 2021 Sci & Tech 0328). Shanghai Municipal Education Commission-Frontier Research Base of Optogenetic Techniques for Cell Metabolism (Y.Z.), Research Unit of New Techniques for Live-cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019-I2M-5-013 to Y.Z.), the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Light-switchable diphtherin transgene system; Losartan; Tumor microenvironment; Breast cancer; Nanoparticle drug delivery system

摘要：Breast cancer is a common malignancy in women. The abnormally dense collagen network in breast cancer forms a therapeutic barrier that hinders the penetration and anti-tumor effect of drugs. To overcome this hurdle, we adopted a therapeutic strategy to treat breast cancer which combined a light-switchable transgene system and losartan. The light-switchable transgene system could regulate expression of the diphtheria toxin A fragment (DTA) gene with a high on/off ratio under blue light and had great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system to achieve tumor microenvironment-responsive and targeted delivery of DTA-encoded plasmids (pDTA) to tumor sites via dual targeting to cluster of differentiation-44 and alpha(v)beta(3) receptors. In vivo studies indicated that the combination of pDTA and losartan reduce the concentration of collagen type I from 5.9 to 1.9 mu g/g and decreased the level of active transforming growth factor-beta by 75.0% in tumor tissues. Moreover, deeper tumor penetration was achieved, tumor growth was inhibited, and the survival rate was increased. Our combination strategy provides a novel and practical method for clinical treatment of breast cancer.