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

Autores de CIPF

• Aroa Duro Castaño

  Autor

• 

  Ana Armiñan De Benito

  Autor

• David Charbonnier

  Autor

• Juan José Arroyo Crespo

  Autor

• 

  Maria Jesus Vicent Docon

  Autor

Participantes ajenos a CIPF

• Sousa-Herves, A
• Wedepohl, S
• Calderon, M

Grupos de Investigación

• Laboratorio de Polímeros Terapéuticos

  

  Jefe/a de Grupo

  Maria Jesus Vicent Docon

Abstract

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.

Keywords

• Polypeptides; Polyglutamic acid; Nanogel; Drug delivery; Triple negative breast Cancer; Lung metastases; Lymph node metastases