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Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity

INTRODUCTION: Here, based on oxygen-dependent photodynamic therapy (PDT) and oxygen-consumed oxidative phosphorylation of cancer tissues, we designed and developed a nanosystem (named CyI&Met-Liposome, LCM) to co-encapsulate the photosensitizer CyI and mitochondrial respiration inhibitor metform...

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Autores principales: Zhao, Yifan, Lv, Bai, Xue, Guanghe, Sun, Yong, Cao, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312333/
https://www.ncbi.nlm.nih.gov/pubmed/37396434
http://dx.doi.org/10.2147/IJN.S413204
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author Zhao, Yifan
Lv, Bai
Xue, Guanghe
Sun, Yong
Cao, Jie
author_facet Zhao, Yifan
Lv, Bai
Xue, Guanghe
Sun, Yong
Cao, Jie
author_sort Zhao, Yifan
collection PubMed
description INTRODUCTION: Here, based on oxygen-dependent photodynamic therapy (PDT) and oxygen-consumed oxidative phosphorylation of cancer tissues, we designed and developed a nanosystem (named CyI&Met-Liposome, LCM) to co-encapsulate the photosensitizer CyI and mitochondrial respiration inhibitor metformin (Met) as a PDT enhancer. METHODS: We synthesized nanoliposomes encapsulating Met and CyI with excellent photodynamic/photothermal and anti-tumor immune properties using a thin film dispersion method. Confocal microscopy and flow cytometry were used to assess the cellular uptake, PDT, photothermal therapy (PTT) and immunogenicity of nanosystem in vitro. Finally, two tumor models in mice were constructed to investigate the tumor suppression and immunity in vivo. RESULTS: The resulting nanosystem relieved hypoxia in tumor tissues, enhanced PDT efficiency, and amplified antitumor immunity induced by phototherapy. As a photosensitizer, CyI effectively killed the tumor by generating toxic singlet reactive oxygen species (ROS), while the addition of Met reduced oxygen consumption in tumor tissues, thereby evoking an immune response via oxygen-boosted PDT. Both in vitro and in vivo results illustrated that LCM effectively restricted the respiration of tumor cells to reduce tumor hypoxia, thus providing continuous oxygen for enhanced CyI-mediated PDT. Furthermore, T cells were recruited and activated at high levels, providing a promising platform to eliminate the primary tumors and synchronously realize effective inhibition of distant tumors.
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spelling pubmed-103123332023-07-01 Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity Zhao, Yifan Lv, Bai Xue, Guanghe Sun, Yong Cao, Jie Int J Nanomedicine Original Research INTRODUCTION: Here, based on oxygen-dependent photodynamic therapy (PDT) and oxygen-consumed oxidative phosphorylation of cancer tissues, we designed and developed a nanosystem (named CyI&Met-Liposome, LCM) to co-encapsulate the photosensitizer CyI and mitochondrial respiration inhibitor metformin (Met) as a PDT enhancer. METHODS: We synthesized nanoliposomes encapsulating Met and CyI with excellent photodynamic/photothermal and anti-tumor immune properties using a thin film dispersion method. Confocal microscopy and flow cytometry were used to assess the cellular uptake, PDT, photothermal therapy (PTT) and immunogenicity of nanosystem in vitro. Finally, two tumor models in mice were constructed to investigate the tumor suppression and immunity in vivo. RESULTS: The resulting nanosystem relieved hypoxia in tumor tissues, enhanced PDT efficiency, and amplified antitumor immunity induced by phototherapy. As a photosensitizer, CyI effectively killed the tumor by generating toxic singlet reactive oxygen species (ROS), while the addition of Met reduced oxygen consumption in tumor tissues, thereby evoking an immune response via oxygen-boosted PDT. Both in vitro and in vivo results illustrated that LCM effectively restricted the respiration of tumor cells to reduce tumor hypoxia, thus providing continuous oxygen for enhanced CyI-mediated PDT. Furthermore, T cells were recruited and activated at high levels, providing a promising platform to eliminate the primary tumors and synchronously realize effective inhibition of distant tumors. Dove 2023-06-26 /pmc/articles/PMC10312333/ /pubmed/37396434 http://dx.doi.org/10.2147/IJN.S413204 Text en © 2023 Zhao et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhao, Yifan
Lv, Bai
Xue, Guanghe
Sun, Yong
Cao, Jie
Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title_full Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title_fullStr Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title_full_unstemmed Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title_short Smart Nanosystem-Mediated Inhibition of Mitochondrial Respiration for Enhanced Phototherapy-Induced Antitumor Immunity
title_sort smart nanosystem-mediated inhibition of mitochondrial respiration for enhanced phototherapy-induced antitumor immunity
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312333/
https://www.ncbi.nlm.nih.gov/pubmed/37396434
http://dx.doi.org/10.2147/IJN.S413204
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