Faculty Collaboration Database

Folate-Targeted Redox-Responsive Polymersomes Loaded with Chemotherapeutic Drugs and Tariquidar to Overcome Drug Resistance. J Biomed Nanotechnol 2018 Oct 01;14(10):1705-1718

Date

07/26/2018

Pubmed ID

30041718

DOI

10.1166/jbn.2018.2623

Scopus ID

2-s2.0-85053638219 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

Tumor multidrug resistance (MDR) is a fatal obstacle to cancer chemotherapy. The combination of P-glycoprotein (P-gp) inhibitor and chemotherapeutic drugs is one of the effective strategies to reverse tumor MDR. Herein, a folate-decorated PCL-ss-PEG-ss-PCL based redox-responsive polymersome (FA-TQR-Co-PS) was constructed, which was loaded with P-gp inhibitor tariquidar (TQR), anticancer drugs doxorubicin (DOX) and paclitaxel (PTX). The results suggested that the FA-TQR-Co-PS with an apparent bilayered lamellar structure displayed good monodispersity, high drug loading capacity, superior stability and redox-stimulated drug release peculiarity. In vitro cellular uptake study demonstrated that FA-TQR-Co-PS increased drug accumulation into MCF-7/ADR cells via the TQR-induced P-gp efflux inhibition, and further improved targeting to tumor cells due to folate receptor-mediated endocytosis. Furthermore, the DOX and PTX cytotoxicity and proapoptotic activity against MCF-7/ADR was enhanced dramatically along with the administration of TQR, and the cell cycle was profoundly blocked in G2/M phase. The folate-targeted redox-responsive polymersomes loaded with chemotherapeutic drugs and P-gp inhibitor demonstrated noticeable synergistic effect against human MDR MCF-7 cells and successfully reversed drug resistance, which displayed high potential in overcoming tumor MDR as a novel drug delivery system.

Author List

Qin Y, Zhang Z, Huang C, Fan F, Liu L, Lu L, Wang H, Liu Z, Yang J, Wang C, Yang H, Sun H, Leng X, Kong D, Zhang L, Zhu D

Author

Hu Yang PhD Chair, Professor in the Biomedical Engineering department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Doxorubicin
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Folic Acid
Humans
MCF-7 Cells
Micelles
Oxidation-Reduction
Quinolines