Light-switchable diphtherin transgene system combined with losartan for triple negtative breast cancer therapy based on nano drug delivery system.
|
| Abstract |
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.
|
|---|---|
| Authors | Yi Cheng, Rui Sun, Muye He, Miao Zhang, Xinyu Hou, Yuji Sun, Jie Wang, Jiajun Xu, Hai He, Hongtao Wang, Minbo Lan, Yuzheng Zhao, Yi Yang, Xianjun Chen, Feng Gao |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 618 Pg. 121613 (Apr 25 2022) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 35217071 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 Elsevier B.V. All rights reserved. |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!