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Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin

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Abstract

Drug efflux induced by multidrug resistance (MDR) overexpression, as well as secondary drug resistance caused by subtoxic drug microenvironments as a result of inefficient drug release of nanoscopic drug carriers in tumor cells, are major bottlenecks for chemotherapy. In order to overcome these limitations, we have devised a synergism-based polymer supramolecular nanoassembly (LH) by combining hyaluronic acid (HA) modified curcumin (HA-CUR) with a pH-sensitive low molecular weight heparin (LMWH) derivative modified doxorubicin (L-DOX). Our study proved that HA modification not only facilitated tumor targeting drug delivery efficiency through CD44 receptors-mediated active tumor-targeting strategy but also significantly enhanced the MDR reversion effect of CUR by improving its biological stability in different physiological environments. Also, the L-DOX in LH could trigger rapid and effective DOX release under a varied pH value environment, thereby overcoming secondary drug resistance. More importantly, a synergistic antitumor effect was achieved by optimizing the ratio of HA-CUR and L-DOX in LH. Furthermore, LH showed a superior therapeutic effect over free DOX in two mouse models of human cancer. Taken together, these results demonstrated that LH might serve as an efficient platform for delivery of therapeutic payloads to overcome MDR.

Graphical abstract: Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin

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Publication details

The article was received on 23 May 2018, accepted on 25 Jul 2018 and first published on 02 Aug 2018


Article type: Paper
DOI: 10.1039/C8BM00570B
Citation: Biomater. Sci., 2018, Advance Article
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    Intracellular self-disassemble polysaccharide nanoassembly for multi-factors tumor drug resistance modulation of doxorubicin

    H. Xiong, J. Ni, Z. Jiang, F. Tian, J. Zhou and J. Yao, Biomater. Sci., 2018, Advance Article , DOI: 10.1039/C8BM00570B

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