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Issue 70, 2019, Issue in Progress
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CD44-targeted hyaluronic acid–curcumin reverses chemotherapeutics resistance by inhibiting P-gp and anti-apoptotic pathways

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Abstract

Chemotherapeutic drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the two most common mechanisms leading to chemotherapy resistance. In this study, we focused on the applicability of curcumin (CUR) as a sensitizer for chemotherapeutics (doxorubicin [DOX] as the model drug) modified with hyaluronic acid (HA) as an effective therapeutic strategy against multidrug resistance (MDR) in cancer cells. We constructed an HA–CUR/DOX delivery system measuring approximately 180 nm with superior encapsulation efficacy and serum stabilities. In vitro, we found that HA modification could facilitate the efficient delivery of chemotherapeutics through CD44 receptor-mediated targeted delivery. MTT assay results confirmed that the combination of CUR and DOX/paclitaxel (PTX) had a significant synergistic effect and significantly reversed MDR. Further experiments including real-time polymerase chain reaction and western blotting proved that the main mechanisms by which CUR reversed MDR in tumor cells were inhibiting the expression and activity of P-glycoprotein (P-gp) and inducing apoptosis through mitochondrial pathway. Taken together, our new engineered tumor-targeting nanoparticle delivery system may have the potential for overcoming MDR in cancer.

Graphical abstract: CD44-targeted hyaluronic acid–curcumin reverses chemotherapeutics resistance by inhibiting P-gp and anti-apoptotic pathways

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Supplementary files

Article information


Submitted
09 Oct 2019
Accepted
02 Dec 2019
First published
11 Dec 2019

This article is Open Access

RSC Adv., 2019,9, 40873-40882
Article type
Paper

CD44-targeted hyaluronic acid–curcumin reverses chemotherapeutics resistance by inhibiting P-gp and anti-apoptotic pathways

L. Diao, A. Shen, Y. Yang, J. Tao and Y. Hu, RSC Adv., 2019, 9, 40873
DOI: 10.1039/C9RA08202F

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