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A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy

Shiwei, N; Williams, G; Jianrong, W; Junzi, W; Xueijing, Z; Hong, Z; Shude, L; (2019) A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy. Chemical Engineering Journal , 369 pp. 134-149. 10.1016/j.cej.2019.02.201. Green open access

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Abstract

In this study, a novel chitosan-based (CS) nanocarrier was developed for doxorubicin (DOX) and oleanolic acid (OA) co-delivery. CS was first functionalized with folic acid to allow selective uptake by cancer cells, and then subsequently with OA. The resultant copolymer self-assembled into nanoparticles (NPs) upon addition to water. These FA-CS-g-OA@DOX nanoparticles (NPs) had appropriate size (180 nm) and size distribution (PDI < 0.45) for tumor therapy, as well as a high drug-loading efficiency (15.6 % w/w DOX; 5.1% w/w OA) and pH-responsive release properties. In breast cancer MDA-MB-231 cells, more efficient uptake of FA-CS-g-OA@DOX NPs than of free DOX was observed by confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of FA-CS-g-OA@DOX NPs against MDA-MB-231 cells was higher than with free DOX and free OA, while the NPs were less harmful to healthy HUVEC cells. In vivo pharmacokinetic studies showed that FA-CS-g-OA@DOX NPs had a much longer circulation time than free DOX, while biodistribution results revealed that FA-CS-g-OA@DOX could actively target a MDA-MB-231 xenograft tumor in mice. The NPs are found to have apoptosis-enhancing and anti-proliferative capacities in vivo. The presence of OA in the formulation both sensitizes cancer cells to DOX and mitigates DOX-induced damage to healthy tissues. The FA-CS-g-OA@DOX NPs generated in this work hence have great potential for the treatment of multi-drug resistant breast cancers, and further offer a platform to target other cancers.

Type: Article
Title: A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cej.2019.02.201
Publisher version: http://doi.org/10.1016/j.cej.2019.02.201
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Chitosan-based nanocarrier; Doxorubicin; Oleanolic acid; Codelivery; Chemosensitizing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
URI: https://discovery.ucl.ac.uk/id/eprint/10069538
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