dc.contributor.author | Duro-Castano, Aroa | |
dc.contributor.author | Sousa-Herves, Ana | |
dc.contributor.author | Armiñán, Ana | |
dc.contributor.author | Charbonnier, David | |
dc.contributor.author | Arroyo-Crespo, Juan José | |
dc.contributor.author | Wedepohl, Stefanie | |
dc.contributor.author | Calderón, Marcelo | |
dc.contributor.author | Vicent, María J. | |
dc.date.accessioned | 2021-02-23T13:38:26Z | |
dc.date.available | 2021-02-23T13:38:26Z | |
dc.date.issued | 2021-02-13 | |
dc.identifier.citation | Journal of Controlled Release 332 : 10-20 (2021) | es_ES |
dc.identifier.issn | 0168-3659 | |
dc.identifier.uri | http://hdl.handle.net/10810/50282 | |
dc.description | Preprint | es_ES |
dc.description.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 signif-icantly 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. | es_ES |
dc.description.sponsorship | A.S-H thanks MC IEF actions (Project 302717). We thank Dr. M. A. Molina for AFM experiments, Ser-vicio SEM Cordoba (Argentina), and Mario Soriano Navarro from the electron microscopy service for Cryo-TEM pictures at CIPF. The authors would also like to thank Dr. Stuart P. Atkinson for his collabo-ration in the revision of the manuscript. This work has been supported by the European Research Council (grant ERC-CoG-2014-648831 “MyNano”), by the Spanish Ministry of Science and Innovation (SAF2013-44848-R, SAF2016-80427-R, RTI2018-099227-B-I00), by a Marie Curie IEF (Project 302717), and the Bundesministerium für Bildung und Forschung (BMBF) through the NanoMatFutur award (13N12561). Part of the equipment employed in this work has been funded by Generalitat Valen-ciana and co-financed with FEDER funds (PO FEDER of Comunitat Valenciana 2014–2020) | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/648831 | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/302717 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIN/SAF2013-44848-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIN/SAF2016-80427-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MCIN/RTI2018-099227-B-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.subject | polypeptides | es_ES |
dc.subject | polyglutamic pcid | es_ES |
dc.subject | nanogel | es_ES |
dc.subject | drug delivery | es_ES |
dc.subject | triple negative breast cancer | es_ES |
dc.subject | lung metastases | es_ES |
dc.subject | lymph node metastases | es_ES |
dc.title | Polyglutamic acid-based Crosslinked Doxorubicin Nanogels as an Anti-Metastatic Treatment for Triple Negative Breast Cancer | es_ES |
dc.type | info:eu-repo/semantics/preprint | es_ES |
dc.rights.holder | © 2021 Published by Elsevier. | es_ES |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/abs/pii/S0168365921000523?via%3Dihub | es_ES |
dc.identifier.doi | 10.1016/j.jconrel.2021.02.005 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Química aplicada | es_ES |
dc.departamentoeu | Kimika aplikatua | es_ES |