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A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy

Niu, S; Williams, GR; Wu, J; Wu, J; Zhang, X; Chen, X; Li, S; ... Zhu, L-M; + view all (2019) A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy. Journal of Nanobiotechnology , 17 , Article 95. 10.1186/s12951-019-0529-4. Green open access

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Abstract

BACKGROUND: It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal. // RESULTS: In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity. // CONCLUSIONS: The system developed in this work has the potential to provide new therapies for hard-to-treat cancers.

Type: Article
Title: A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12951-019-0529-4
Publisher version: https://doi.org/10.1186/s12951-019-0529-4
Language: English
Additional information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Chitosan, Doxorubicin, Triple-negative breast, Cascade responsive, Cell penetrating peptide
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/10081455
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