Issue 10, 2017

pH and redox dual-sensitive polysaccharide nanoparticles for the efficient delivery of doxorubicin

Abstract

A pH and redox dual-sensitive biodegradable polysaccharide, succinic acid-decorated dextran-g-phenylalanine ethyl ester-g-cysteine ethyl ester (Dex-SA-L-Phe-L-Cys), was synthesized to load doxorubicin hydrochloride (DOX·HCl). The DOX-loaded nanoparticles, which were prepared in aqueous solution and free of organic solvent, could spontaneously self-assemble into uniform sizes. When loading DOX·HCl, mercapto Dex-SA-L-Phe-L-Cys was oxidized into a crosslinked disulfide linkage to form pH and redox dual-sensitive nanoparticles (DOX-S-NPs). The amphiphilic polymer loaded DOX·HCl into the core through electrostatic and hydrophobic interactions, meanwhile the crosslinked disulfide bond could stabilize the drug loaded nanoparticles. As a control with similar polymer structure, succinic acid decorated dextran-g-phenylalanine ethyl ester (Dex-SA-L-Phe) was prepared to obtain pH-sensitive DOX-loaded micelles (DOX-N-NPs). The controlled pH and redox-dependent release profiles of the DOX-S-NPs in vitro were certified in different releasing mediums. Furthermore, the cellular uptake of the DOX-S-NPs was comparable with that of free DOX·HCl, determined by confocal laser scanning microscopy (CLSM) and flow cytometry. Cytotoxicity assay in vitro showed that the DOX-S-NPs and free DOX·HCl were similar in inhibiting the proliferation of non-small cell lung carcinoma A549 and breast cancer MCF-7 cell lines. DOX-S-NPs displayed similar antitumor efficiency compared with free DOX·HCl, but lower toxicity by body weight. These dual-sensitive DOX-S-NPs provide a useful strategy for anti-tumor therapy.

Graphical abstract: pH and redox dual-sensitive polysaccharide nanoparticles for the efficient delivery of doxorubicin

Article information

Article type
Paper
Submitted
18 Jul 2017
Accepted
31 Aug 2017
First published
04 Sep 2017

Biomater. Sci., 2017,5, 2169-2178

pH and redox dual-sensitive polysaccharide nanoparticles for the efficient delivery of doxorubicin

S. Yang, Z. Tang, D. Zhang, M. Deng and X. Chen, Biomater. Sci., 2017, 5, 2169 DOI: 10.1039/C7BM00632B

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