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Core/shell stabilized polysaccharide-based nanoparticle with intracellular environment-sensitive drug delivery for breast cancer therapy

Abstract

In this work, we developed a novel core/shell chitosan (Cs)/hyaluronan (HA)-based hybrid nanoparticle, i.e. SNX@Cs-SNX/cHA, with good stability in the bloodstream and intracellular environment-sensitive drug delivery for breast cancer therapy. The core was drug-loaded self-assembled micelle (SNX@Cs-SNX), and the shell was crosslinked cysteine-conjugated hyaluronan (cHA) by disulfide bonds. Thanks to the combination of chemical bonding and physical encapsulation, the drug loading capacity of SNX@Cs-SNX/cHA nanoparticles was up to (14.6 ± 0.3)% in mass percentage. These stabilized core/shell nanoparticles were little affected by ionic strength (0.05~1.0 M sodium chloride solution), pH (6.8 and 7.4) and human plasma mimicking the bloodstream, but promptly disassembled by the multi-stimuli of glutathione (GSH), hyaluronidases (Hyals) and acidity (pH 5.0) mimicking the intracellular environment of breast cancer cells. In vitro 84% of loaded drugs was released by GSH/Hyals/pH multi-stimuli within 72 h, as opposed to 28% at pH 7.4. SNX@Cs-SNX/cHA nanoparticles were highly endocytosed by both MCF-7 and MDA-MB-453 breast cancer cells and escaped from the endosomes/lysosomes by confocal laser scanning microscopy, showing a close IC50 value of 24.5 ng/mL and 41.0 ng/mL respectively to pure SNX. Thus, SNX@Cs-SNX/cHA nanoparticle, which can not only increase the drug loading ability and stability in the blood circulation, but also control the fast intracellular drug delivery by GSH/Hyals/pH multi-stimuli in breast cancer cells, is a potential drug carrier for breast cancer therapy.

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Publication details

The article was received on 07 Mar 2018, accepted on 14 Sep 2018 and first published on 15 Sep 2018


Article type: Paper
DOI: 10.1039/C8TB00633D
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Core/shell stabilized polysaccharide-based nanoparticle with intracellular environment-sensitive drug delivery for breast cancer therapy

    Y. Wu, X. Zhang, H. Li, P. Deng, H. Li, T. He, J. Rong, J. Zhao and Z. Liu, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB00633D

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