癌症研究
乳腺癌
氯沙坦
药物输送
转基因
肿瘤微环境
体内
遗传增强
癌症
白喉毒素
基因传递
医学
化学
生物
受体
内科学
基因
生物化学
毒素
生物技术
血管紧张素II
有机化学
作者
Cheng Yi,Rui Sun,Muye He,Miao Zhang,Xinyu Hou,Yuji Sun,Jie Wang,Jiajun Xu,Hai He,Qingyuan Wang,Minbo Lan,Yuzheng Zhao,Yi Yang,Xianjun Chen,Feng Gao
标识
DOI:10.1016/j.ijpharm.2022.121613
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 αvβ3 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 µg/g and decreased the level of active transforming growth factor-β 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI