期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 229, 期 -, 页码 600-614出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2022.12.266
关键词
Co-delivery; Mesoporous silica nanoparticles; Drug-resistant TNBC; Aptamer; siRNA; Drug
In this study, a multifunctional nanocarrier based on mesoporous silica nanoparticles was developed for co-delivery against drug-resistant triple-negative breast cancer cells. The results showed that the co-delivery of doxorubicin and siRNA using this nanocarrier exhibited significant cytotoxic efficacy and had the potential to overcome drug resistance in breast cancer cells.
The emergence of drug resistance in cancer cells is among the major challenges for treating cancer. In the last few years, the co-delivery of drug and siRNA has shown promising results against drug-resistant cancers. In the present study, we developed mesoporous silica-based multifunctional nanocarrier for co-delivery against drug -resistant triple-negative breast cancer (TNBC) cells. We synthesized the nanocarrier by modifying mesoporous silica nanoparticles with poly-L-arginine, polyethylene glycol and AS1411 aptamer to impart siRNA binding ability, biocompatibility, and cancer cell specificity, respectively. We optimized the loading of doxorubicin (DOX) within the developed nanocarrier to avoid interference with siRNA binding. We ascertained the target specificity by performing a receptor blockade assay during cellular uptake studies. The cytotoxic efficacy of DOX and siRNA co-delivered using the developed nanocarrier was assessed using DOX-resistant MDA-MB-231 TNBC cells. The nanocarrier exhibited >10-fold and 40-fold reduction in the IC50 values of DOX due to co-delivery with BCl-xL and BCL-2 siRNA, respectively. The results were further validated using a 3-D in vitro cell culture system. This study demonstrates that the targeted co-delivery of drug and siRNA has a strong potential to overcome drug resistance in TNBC cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据