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Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier

[Image: see text] Integration of photosensitizers (PSs) within nanoscale delivery systems offers great potential for overcoming some of the “Achiles’ heels” of photodynamic therapy (PDT). Herein, we have encapsulated a mitochondria-targeted coumarin PS into amphoteric polyurethane–polyurea hybrid na...

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Autores principales: Bonelli, Joaquín, Ortega-Forte, Enrique, Rovira, Anna, Bosch, Manel, Torres, Oriol, Cuscó, Cristina, Rocas, Josep, Ruiz, José, Marchán, Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277592/
https://www.ncbi.nlm.nih.gov/pubmed/35695426
http://dx.doi.org/10.1021/acs.biomac.2c00361
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author Bonelli, Joaquín
Ortega-Forte, Enrique
Rovira, Anna
Bosch, Manel
Torres, Oriol
Cuscó, Cristina
Rocas, Josep
Ruiz, José
Marchán, Vicente
author_facet Bonelli, Joaquín
Ortega-Forte, Enrique
Rovira, Anna
Bosch, Manel
Torres, Oriol
Cuscó, Cristina
Rocas, Josep
Ruiz, José
Marchán, Vicente
author_sort Bonelli, Joaquín
collection PubMed
description [Image: see text] Integration of photosensitizers (PSs) within nanoscale delivery systems offers great potential for overcoming some of the “Achiles’ heels” of photodynamic therapy (PDT). Herein, we have encapsulated a mitochondria-targeted coumarin PS into amphoteric polyurethane–polyurea hybrid nanocapsules (NCs) with the aim of developing novel nanoPDT agents. The synthesis of coumarin-loaded NCs involved the nanoemulsification of a suitable prepolymer in the presence of a PS without needing external surfactants, and the resulting small nanoparticles showed improved photostability compared with the free compound. Nanoencapsulation reduced dark cytotoxicity of the coumarin PS and significantly improved in vitro photoactivity with red light toward cancer cells, which resulted in higher phototherapeutic indexes compared to free PS. Importantly, this nanoformulation impaired tumoral growth of clinically relevant three-dimensional multicellular tumor spheroids. Mitochondrial photodamage along with reactive oxygen species (ROS) photogeneration was found to trigger autophagy and apoptotic cell death of cancer cells.
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spelling pubmed-92775922022-07-14 Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier Bonelli, Joaquín Ortega-Forte, Enrique Rovira, Anna Bosch, Manel Torres, Oriol Cuscó, Cristina Rocas, Josep Ruiz, José Marchán, Vicente Biomacromolecules [Image: see text] Integration of photosensitizers (PSs) within nanoscale delivery systems offers great potential for overcoming some of the “Achiles’ heels” of photodynamic therapy (PDT). Herein, we have encapsulated a mitochondria-targeted coumarin PS into amphoteric polyurethane–polyurea hybrid nanocapsules (NCs) with the aim of developing novel nanoPDT agents. The synthesis of coumarin-loaded NCs involved the nanoemulsification of a suitable prepolymer in the presence of a PS without needing external surfactants, and the resulting small nanoparticles showed improved photostability compared with the free compound. Nanoencapsulation reduced dark cytotoxicity of the coumarin PS and significantly improved in vitro photoactivity with red light toward cancer cells, which resulted in higher phototherapeutic indexes compared to free PS. Importantly, this nanoformulation impaired tumoral growth of clinically relevant three-dimensional multicellular tumor spheroids. Mitochondrial photodamage along with reactive oxygen species (ROS) photogeneration was found to trigger autophagy and apoptotic cell death of cancer cells. American Chemical Society 2022-06-13 2022-07-11 /pmc/articles/PMC9277592/ /pubmed/35695426 http://dx.doi.org/10.1021/acs.biomac.2c00361 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Bonelli, Joaquín
Ortega-Forte, Enrique
Rovira, Anna
Bosch, Manel
Torres, Oriol
Cuscó, Cristina
Rocas, Josep
Ruiz, José
Marchán, Vicente
Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title_full Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title_fullStr Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title_full_unstemmed Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title_short Improving Photodynamic Therapy Anticancer Activity of a Mitochondria-Targeted Coumarin Photosensitizer Using a Polyurethane–Polyurea Hybrid Nanocarrier
title_sort improving photodynamic therapy anticancer activity of a mitochondria-targeted coumarin photosensitizer using a polyurethane–polyurea hybrid nanocarrier
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277592/
https://www.ncbi.nlm.nih.gov/pubmed/35695426
http://dx.doi.org/10.1021/acs.biomac.2c00361
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