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

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...

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Bibliographic Details
Published inJournal of controlled release Vol. 332; pp. 10 - 20
Main Authors Duro-Castano, Aroa, Sousa-Herves, Ana, Armiñán, Ana, Charbonnier, David, Arroyo-Crespo, Juan José, Wedepohl, Stefanie, Calderón, Marcelo, Vicent, María J.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 10.04.2021
Subjects
Drug delivery
Lung metastases
Lymph node metastases
Nanogel
Polyglutamic acid
Polypeptides
Triple negative breast Cancer
Lung metastases
Triple negative breast Cancer
Polypeptides
Nanogel
Lymph node metastases
Drug delivery
Polyglutamic acid
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Summary: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 ~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. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2021.02.005