期刊
JOURNAL OF CONTROLLED RELEASE
卷 332, 期 -, 页码 10-20出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2021.02.005
关键词
Polypeptides; Polyglutamic acid; Nanogel; Drug delivery; Triple negative breast Cancer; Lung metastases; Lymph node metastases
资金
- Marie Curie IEF actions [302717]
- European Research Council [ERC-CoG-2014-648831]
- Spanish Ministry of Science and Innovation [SAF2013-44848-R, SAF2016-80427-R, RTI2018-099227-B-I00]
- Bundesministerium fur Bildung und Forschung (BMBF) through the NanoMatFutur award [13N12561]
- Generalitat Valenciana
- FEDER funds (PO FEDER of Comunitat Valenciana 2014-2020)
The research team utilized poly-amino acid-based nanogels (NGs) as a drug delivery platform to successfully inhibit TNBC lung metastasis and almost completely suppress lymph node metastasis in a mouse model.
Treatment of triple negative breast cancer (TNBC)-associated metastasis represents an unmet clinical need, and we lack effective therapeutics for a disease that exhibits high relapse rates and associates with poor patient outcomes. Advanced nanosized drug delivery systems may enhance the efficacy of first-line chemotherapeutics by altering drug pharmacokinetics and enhancing tumor/metastasis targeting to significantly improve efficacy and safety. Herein, we propose the application of injectable poly-amino acid-based nanogels (NGs) as a versatile hydrophilic drug delivery platform for the treatment of TNBC lung metastasis. We prepared biocompatible and biodegradable cross-linked NGs from polyglutamic acid (PGA) loaded with the chemotherapeutic agent doxorubicin (DOX). Our optimized synthetic procedures generated NGs of similar to 100 nm in size and 25 wt% drug loading content that became rapidly internalized in TNBC cell lines and displayed IC50 values comparable to the free form of DOX. Importantly, PGA-DOX NGs significantly inhibited lung metastases and almost completely suppressed lymph node metastases in a spontaneously metastatic orthotopic mouse TNBC model. Overall, our newly developed PGA-DOX NGs represent a potentially effective therapeutic strategy for the treatment of TNBC metastases.
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