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- Title
A chitosan-based cascade-responsive drug delivery system for triple-negative breast cancer therapy.
- Authors
Niu, Shiwei; Williams, Gareth R.; Wu, Jianrong; Wu, Junzi; Zhang, Xuejing; Chen, Xia; Li, Shude; Jiao, Jianlin; Zhu, Li-Min
- 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.
- Subjects
TRIPLE-negative breast cancer; DRUG delivery systems; CANCER treatment; CHITOSAN; DOXORUBICIN; HIGH temperature physics; TUMOR microenvironment
- Publication
Journal of Nanobiotechnology, 2019, Vol 17, Issue 1, pN.PAG
- ISSN
1477-3155
- Publication type
Article
- DOI
10.1186/s12951-019-0529-4