UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Stimuli-responsive polymeric prodrug-based nanomedicine delivering nifuroxazide and doxorubicin against primary breast cancer and pulmonary metastasis

Luo, L; Xu, F; Peng, H; Luo, Y; Tian, X; Battaglia, G; Zhang, H; ... Luo, K; + view all (2020) Stimuli-responsive polymeric prodrug-based nanomedicine delivering nifuroxazide and doxorubicin against primary breast cancer and pulmonary metastasis. Journal of Controlled Release , 318 pp. 124-135. 10.1016/j.jconrel.2019.12.017. Green open access

[thumbnail of 1-s2.0-S0168365919307369-main.pdf]
Preview
Text
1-s2.0-S0168365919307369-main.pdf - Accepted Version

Download (2MB) | Preview

Abstract

Functionalized drug delivery systems against malignant lung metastasis of breast cancer have been extensively studied, while metastasis remains a challenging issue. We propose a new strategy to achieve eradication of primary breast cancer cells and inhibition of pulmonary metastasis. A cathepsin B/pH dual-sensitive block copolymer with a molecular weight of 92 kDa was synthesized to conjugate with doxorubicin (DOX). The copolymer-DOX was further loaded with nifuroxazide (NFX) to self-assemble co-prodrug-loaded micelles (CLM). CLM displayed a drug release pattern in response to pH/enzyme dual stimuli and was enzymatically biodegradable. CLM was demonstrated to reduce viability and inhibit migration and invasion of 4T1 murine breast cancer cells in vitro. After i.v. injection of CLM, its nanoscale size and stimuli-responsiveness facilitated delivery of drugs to the tumor site in mice. Enhanced anti-tumor efficacy and great anti-metastatic effects were found in both orthotropic and lung metastasis 4T1 breast cancer mice models. Meanwhile, histological immunofluorescence and immunohistochemical analyses revealed a high level of apoptosis, suppressed expression of matrix metalloproteinases and reduction in MDSCs infiltration, and all these contributed to inhibit pulmonary metastasis. CLM may be explored as a potential nanomedicine against breast cancer metastasis.

Type: Article
Title: Stimuli-responsive polymeric prodrug-based nanomedicine delivering nifuroxazide and doxorubicin against primary breast cancer and pulmonary metastasis
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jconrel.2019.12.017
Publisher version: https://doi.org/10.1016/j.jconrel.2019.12.017
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: Breast metastasis, Controlled release, Drug delivery, Polymeric prodrug, Stimuli-responsive
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10088648
Downloads since deposit
461Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item