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.
Recommended Citation
Y. Qin et al., "Folate-Targeted Redox-Responsive Polymersomes Loaded with Chemotherapeutic Drugs and Tariquidar to overcome Drug Resistance," Journal of Biomedical Nanotechnology, vol. 14, no. 10, pp. 1705 - 1718, American Scientific Publishers, Oct 2018.
The definitive version is available at https://doi.org/10.1166/jbn.2018.2623
Department(s)
Chemical and Biochemical Engineering
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
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).