文献类型：期刊文献

英文题名：Spatiotemporally controlled Pseudomonas exotoxin transgene system combined with multifunctional nanoparticles for breast cancer antimetastatic therapy

作者：Cheng, Yi[1,2,3];Zou, Jiafeng[1,2,3];He, Muye[1];Hou, Xinyu[1];Wang, Hongtao[1];Xu, Jiajun[1];Yuan, Zeting[1];Lan, Minbo[2];Yang, Yi[1,4,6];Chen, Xianjun[1,4,5,6,8];Gao, Feng[1,2,3,4,7]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai 200237, 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 Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[6]Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing 100050, 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：2024

卷号：367

起止页码：167

外文期刊名：JOURNAL OF CONTROLLED RELEASE

收录：;EI(收录号：20240515450765);WOS:【SCI-EXPANDED(收录号:WOS:001175232100001)】；

基金：Development Program of China (contract No.2019YFA0904800) , National Natural 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 03-28) . 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：Spatiotemporally controlled gene expression; cancer -associated fibroblasts; Multifunctional nanoparticles; Pseudomonas exotoxin A; Antimetastasis therapy; Breast cancer

摘要：The tumor microenvironment is a barrier to breast cancer therapy. Cancer-associated fibroblast cells (CAFs) can support tumor proliferation, metastasis, and drug resistance by secreting various cytokines and growth factors. Abnormal angiogenesis provides sufficient nutrients for tumor proliferation. Considering that CAFs express the sigma receptor (which recognizes anisamide, AA), we developed a CAFs and breast cancer cells dual-targeting nano drug delivery system to transport the LightOn gene express system, a spatiotemporal controlled gene expression consisting of a light-sensitive transcription factor and a specific minimal promoter. We adopted RGD (Arg-Gly-Asp) to selectively bind to the alpha v beta 3 integrin on activated vascular endothelial cells and tumor cells. After the LightOn system has reached the tumor site, LightOn gene express system can spatiotemporal controllably express toxic Pseudomonas exotoxin An under blue light irradiation. The LightOn gene express system, combined with multifunctional nanoparticles, achieved high targeting delivery efficiency both in vitro and in vivo. It also displayed strong tumor and CAFs inhibition, anti-angiogenesis ability and anti-metastasis ability, with good safety. Moreover, it improved survival rate, survival time, and lung metastasis rate in a mouse breast cancer model. This study proves the efficacy of combining the LightOn system with targeted multifunctional nanoparticles in tumor and anti-metastatic therapy and provides new insights into tumor microenvironment regulation.