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Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug

Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug conce...

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Autores principales: Pérez-Hernández, Marta, Cuscó, Cristina, Benítez-García, Cristina, Bonelli, Joaquin, Nuevo-Fonoll, Marina, Soriano, Aroa, Martínez-García, David, Arias-Betancur, Alain, García-Valverde, María, Segura, Miguel F., Quesada, Roberto, Rocas, Josep, Soto-Cerrato, Vanessa, Pérez-Tomás, Ricardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147975/
https://www.ncbi.nlm.nih.gov/pubmed/34064518
http://dx.doi.org/10.3390/biomedicines9050508
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author Pérez-Hernández, Marta
Cuscó, Cristina
Benítez-García, Cristina
Bonelli, Joaquin
Nuevo-Fonoll, Marina
Soriano, Aroa
Martínez-García, David
Arias-Betancur, Alain
García-Valverde, María
Segura, Miguel F.
Quesada, Roberto
Rocas, Josep
Soto-Cerrato, Vanessa
Pérez-Tomás, Ricardo
author_facet Pérez-Hernández, Marta
Cuscó, Cristina
Benítez-García, Cristina
Bonelli, Joaquin
Nuevo-Fonoll, Marina
Soriano, Aroa
Martínez-García, David
Arias-Betancur, Alain
García-Valverde, María
Segura, Miguel F.
Quesada, Roberto
Rocas, Josep
Soto-Cerrato, Vanessa
Pérez-Tomás, Ricardo
author_sort Pérez-Hernández, Marta
collection PubMed
description Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands.
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spelling pubmed-81479752021-05-26 Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug Pérez-Hernández, Marta Cuscó, Cristina Benítez-García, Cristina Bonelli, Joaquin Nuevo-Fonoll, Marina Soriano, Aroa Martínez-García, David Arias-Betancur, Alain García-Valverde, María Segura, Miguel F. Quesada, Roberto Rocas, Josep Soto-Cerrato, Vanessa Pérez-Tomás, Ricardo Biomedicines Article Cancer is one of the leading causes of mortality worldwide due, in part, to limited success of some current therapeutic approaches. The clinical potential of many promising drugs is restricted by their systemic toxicity and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we developed a novel drug delivery system based on polyurea/polyurethane nanocapsules (NCs) showing pH-synchronized amphoteric properties that facilitate their accumulation and selectivity into acidic tissues, such as tumor microenvironment. We have demonstrated that the anticancer drug used in this study, a hydrophobic anionophore named T21, increases its cytotoxic activity in acidic conditions when nanoencapsulated, which correlates with a more efficient cellular internalization. A biodistribution assay performed in mice has shown that the NCs are able to reach the tumor and the observed systemic toxicity of the free drug is significantly reduced in vivo when nanoencapsulated. Additionally, T21 antitumor activity is preserved, accompanied by tumor mass reduction compared to control mice. Altogether, this work shows these NCs as a potential drug delivery system able to reach the tumor microenvironment, reducing the undesired systemic toxic effects. Moreover, these nanosystems are prepared under scalable methodologies and straightforward process, and provide tumor selectivity through a smart mechanism independent of targeting ligands. MDPI 2021-05-04 /pmc/articles/PMC8147975/ /pubmed/34064518 http://dx.doi.org/10.3390/biomedicines9050508 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pérez-Hernández, Marta
Cuscó, Cristina
Benítez-García, Cristina
Bonelli, Joaquin
Nuevo-Fonoll, Marina
Soriano, Aroa
Martínez-García, David
Arias-Betancur, Alain
García-Valverde, María
Segura, Miguel F.
Quesada, Roberto
Rocas, Josep
Soto-Cerrato, Vanessa
Pérez-Tomás, Ricardo
Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title_full Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title_fullStr Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title_full_unstemmed Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title_short Multi-Smart and Scalable Bioligands-Free Nanomedical Platform for Intratumorally Targeted Tambjamine Delivery, a Difficult to Administrate Highly Cytotoxic Drug
title_sort multi-smart and scalable bioligands-free nanomedical platform for intratumorally targeted tambjamine delivery, a difficult to administrate highly cytotoxic drug
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147975/
https://www.ncbi.nlm.nih.gov/pubmed/34064518
http://dx.doi.org/10.3390/biomedicines9050508
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