Issue 21, 2022

Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

Abstract

Multidrug resistance (MDR) has become one of the most intractable problems in clinics as it would cause failure in chemotherapy. In this study, we demonstrated that a nanoscale self-assembled nanomedicine, which almost consisted of a pure chemo-drug, could efficiently overcome MDR. Celastrol (CST) was directly assembled into a discrete nanomedicine by precipitation, and then CST nanoparticles (CNPs) inhibited drug efflux pumps by activating HSF-1 expression and promoting HSF-1 translocation into nucleus to suppress the Pgp expression. The more drug accumulated in cells could activate apoptosis signals simultaneously and realize drug resistance reversal. CNPs significantly increased the level of ROS to regulate ERK/JNK signaling, which would further induce resistant cell apoptosis. The tandem apoptosis strategy used the same concentration of CST but achieved a higher antitumor effect. Overall, our study provides a new translational and alternative strategy using conventional natural products to overcome MDR with high efficacy.

Graphical abstract: Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

Supplementary files

Article information

Article type
Paper
Submitted
15 Apr 2022
Accepted
05 May 2022
First published
18 May 2022

Nanoscale, 2022,14, 7856-7863

Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine

Y. Xiao, X. Li, J. Mao, H. Zheng, R. Ji, Z. Wang, M. Guo, H. Yuan, A. Anwar, C. Chen, X. Liu and J. Liu, Nanoscale, 2022, 14, 7856 DOI: 10.1039/D2NR02064E

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