4.8 Article

Polyglutamic acid-based crosslinked doxorubicin nanogels as an anti-metastatic treatment for triple negative breast cancer

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

  1. Marie Curie IEF actions [302717]
  2. European Research Council [ERC-CoG-2014-648831]
  3. Spanish Ministry of Science and Innovation [SAF2013-44848-R, SAF2016-80427-R, RTI2018-099227-B-I00]
  4. Bundesministerium fur Bildung und Forschung (BMBF) through the NanoMatFutur award [13N12561]
  5. Generalitat Valenciana
  6. FEDER funds (PO FEDER of Comunitat Valenciana 2014-2020)

向作者/读者索取更多资源

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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