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Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas

Sarcomas are aggressive tumors which often show a poor response to current treatments. As a promising therapeutic alternative, we focused on mithramycin (MTM), a natural antibiotic with a promising anti-tumor activity but also a relevant systemic toxicity. Therefore, the encapsulation of MTM in nano...

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Autores principales: Estupiñán, Óscar, Rendueles, Claudia, Suárez, Paula, Rey, Verónica, Murillo, Dzohara, Morís, Francisco, Gutiérrez, Gemma, Blanco-López, María del Carmen, Matos, María, Rodríguez, René
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037461/
https://www.ncbi.nlm.nih.gov/pubmed/33806182
http://dx.doi.org/10.3390/jcm10071358
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author Estupiñán, Óscar
Rendueles, Claudia
Suárez, Paula
Rey, Verónica
Murillo, Dzohara
Morís, Francisco
Gutiérrez, Gemma
Blanco-López, María del Carmen
Matos, María
Rodríguez, René
author_facet Estupiñán, Óscar
Rendueles, Claudia
Suárez, Paula
Rey, Verónica
Murillo, Dzohara
Morís, Francisco
Gutiérrez, Gemma
Blanco-López, María del Carmen
Matos, María
Rodríguez, René
author_sort Estupiñán, Óscar
collection PubMed
description Sarcomas are aggressive tumors which often show a poor response to current treatments. As a promising therapeutic alternative, we focused on mithramycin (MTM), a natural antibiotic with a promising anti-tumor activity but also a relevant systemic toxicity. Therefore, the encapsulation of MTM in nano-delivery systems may represent a way to increase its therapeutic window. Here, we designed novel transfersomes and PLGA polymeric micelles by combining different membrane components (phosphatidylcholine, Span 60, Tween 20 and cholesterol) to optimize the nanoparticle size, polydispersity index (PDI) and encapsulation efficiency (EE). Using both thin film hydration and the ethanol injection methods we obtained MTM-loaded transferosomes displaying an optimal hydrodynamic diameter of 100–130 nm and EE values higher than 50%. Additionally, we used the emulsion/solvent evaporation method to synthesize polymeric micelles with a mean size of 228 nm and a narrow PDI, capable of encapsulating MTM with EE values up to 87%. These MTM nano-delivery systems mimicked the potent anti-tumor activity of free MTM, both in adherent and cancer stem cell-enriched tumorsphere cultures of myxoid liposarcoma and chondrosarcoma models. Similarly to free MTM, nanocarrier-delivered MTM efficiently inhibits the signaling mediated by the pro-oncogenic factor SP1. In summary, we provide new formulations for the efficient encapsulation of MTM which may constitute a safer delivering alternative to be explored in future clinical uses.
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spelling pubmed-80374612021-04-12 Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas Estupiñán, Óscar Rendueles, Claudia Suárez, Paula Rey, Verónica Murillo, Dzohara Morís, Francisco Gutiérrez, Gemma Blanco-López, María del Carmen Matos, María Rodríguez, René J Clin Med Article Sarcomas are aggressive tumors which often show a poor response to current treatments. As a promising therapeutic alternative, we focused on mithramycin (MTM), a natural antibiotic with a promising anti-tumor activity but also a relevant systemic toxicity. Therefore, the encapsulation of MTM in nano-delivery systems may represent a way to increase its therapeutic window. Here, we designed novel transfersomes and PLGA polymeric micelles by combining different membrane components (phosphatidylcholine, Span 60, Tween 20 and cholesterol) to optimize the nanoparticle size, polydispersity index (PDI) and encapsulation efficiency (EE). Using both thin film hydration and the ethanol injection methods we obtained MTM-loaded transferosomes displaying an optimal hydrodynamic diameter of 100–130 nm and EE values higher than 50%. Additionally, we used the emulsion/solvent evaporation method to synthesize polymeric micelles with a mean size of 228 nm and a narrow PDI, capable of encapsulating MTM with EE values up to 87%. These MTM nano-delivery systems mimicked the potent anti-tumor activity of free MTM, both in adherent and cancer stem cell-enriched tumorsphere cultures of myxoid liposarcoma and chondrosarcoma models. Similarly to free MTM, nanocarrier-delivered MTM efficiently inhibits the signaling mediated by the pro-oncogenic factor SP1. In summary, we provide new formulations for the efficient encapsulation of MTM which may constitute a safer delivering alternative to be explored in future clinical uses. MDPI 2021-03-25 /pmc/articles/PMC8037461/ /pubmed/33806182 http://dx.doi.org/10.3390/jcm10071358 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Estupiñán, Óscar
Rendueles, Claudia
Suárez, Paula
Rey, Verónica
Murillo, Dzohara
Morís, Francisco
Gutiérrez, Gemma
Blanco-López, María del Carmen
Matos, María
Rodríguez, René
Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title_full Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title_fullStr Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title_full_unstemmed Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title_short Nano-Encapsulation of Mithramycin in Transfersomes and Polymeric Micelles for the Treatment of Sarcomas
title_sort nano-encapsulation of mithramycin in transfersomes and polymeric micelles for the treatment of sarcomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037461/
https://www.ncbi.nlm.nih.gov/pubmed/33806182
http://dx.doi.org/10.3390/jcm10071358
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