Polyglutamic acid-based crosslinked doxorubicin nanogels as an anti-metastatic treatment for triple negative breast cancer
Por:
A. DURO-CASTANO, A. SOUSA-HERVES, A. ARMINAN, D. CHARBONNIER, J. ARROYO-CRESPO, S. WEDEPOHL, M. CALDERON and M. VICENT
Publicada:
10 abr 2021
Ahead of Print:
1 feb 2021
Resumen:
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.
Filiaciones:
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Eduardo Primo Yufera 3, Valencia 46012, Spain
A. SOUSA-HERVES:
Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin, Germany
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Eduardo Primo Yufera 3, Valencia 46012, Spain
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Eduardo Primo Yufera 3, Valencia 46012, Spain
S. WEDEPOHL:
Free Univ Berlin, Inst Chem & Biochem, Takustr 3, D-14195 Berlin, Germany
M. CALDERON:
Univ Basque Country, Fac Chem, UPV EHU, POLYMAT, Paseo Manuel de Lardizabal 3, Donostia San Sebastian 20018, Spain
Univ Basque Country, Fac Chem, UPV EHU, Appl Chem Dept, Paseo Manuel de Lardizabal 3, Donostia San Sebastian 20018, Spain
IKERBASQUE, Basque Fdn Sci, Bilbao 48013, Spain
:
Ctr Invest Principe Felipe, Polymer Therapeut Lab, Eduardo Primo Yufera 3, Valencia 46012, Spain
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