Jump to main content
Jump to site search


Intracellular Self-disassemble Polysaccharide Nanosssembly for Multi-factors Tumor Drug Resistance Modulation of Doxorubicin

Abstract

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

Back to tab navigation

Supplementary files

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, Accepted Manuscript
  •   Request permissions

    Intracellular Self-disassemble Polysaccharide Nanosssembly 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, Accepted Manuscript , DOI: 10.1039/C8BM00570B

Search articles by author

Spotlight

Advertisements