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pH-responsive prodrug nanoparticles based on a sodium alginate derivative for selective co-release of doxorubicin and curcumin in tumor cells

Abstract

In order to realize a combination chemotherapy and selective drug release in tumor cells, novel pH-sensitive prodrug nanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells. Additionally, a second chemotherapeutic agent, Cur, was encapsulated in the core of nanoparticles (Cur-Dox-NPs) via the hydrophobic effects, with a significant drug loading capacity. Cur-Dox-NPs exhibited an efficient release of both Dox and Cur in acidic media and further studies of their intracellular uptake and drug release confirmed that the Dox-NPs were easily taken up by cells and selectively released drug in human breast cancer cell line MCF-7. In vitro cytotoxicity studies of the NPs showed a remarkable efficacy against MCF-7 cell lines, whereas an improved safety profile was observed in human breast epithelial cell line MCF-10A. Furthermore, in vivo studies in zebrafish further confirmed an efficient absorption of Dox-NPs. In vivo cardiotoxicity experiments on a zebrafish model showed that Dox-NPs exhibited an improved cardiotoxicity profile in comparison with free Dox. This study demonstrated that this novel pH-sensitive prodrug nanoparticle system may provide a simple and efficient platform for selective co-delivery of multiple drugs to tumor cells.

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Supplementary files

Publication details

The article was received on 21 May 2017, accepted on 27 Jul 2017 and first published on 28 Jul 2017


Article type: Paper
DOI: 10.1039/C7NR03611F
Citation: Nanoscale, 2017, Accepted Manuscript
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    pH-responsive prodrug nanoparticles based on a sodium alginate derivative for selective co-release of doxorubicin and curcumin in tumor cells

    C. Gao, F. Tang, G. Gong, J. Zhang, M. P. M. Hoi, S. M. Lee and R. Wang, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C7NR03611F

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