Folate-Targeted Redox-Responsive Polymersomes Loaded with Chemotherapeutic Drugs and Tariquidar to overcome Drug Resistance

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.

Department(s)

Chemical and Biochemical Engineering

Comments

The work was supported, in part, by National Natural Science Foundation of China (81571793, 81671806, 31670948, 81671694), CAMS Innovation Fund for Medical Sciences (2017-I2M-3-020 and 2017-I2M-4-001), Tianjin Municipal Natural Science Foundation (15JCZDJC38300 and 15JCQNJC46200).

Keywords and Phrases

Combination Therapy; Drug Resistance; Polymersome; Redox-Responsive; Tariquidar

International Standard Serial Number (ISSN)

1550-7033; 1550-7041

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2018 American Scientific Publishers, All rights reserved.

Publication Date

01 Oct 2018

PubMed ID

30041718

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