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Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem
Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490505/ https://www.ncbi.nlm.nih.gov/pubmed/34646381 http://dx.doi.org/10.7150/thno.62984 |
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author | Ren, Junjie Zhou, Jing Liu, Han Jiao, Xiaodan Cao, Yang Xu, Zhigang Kang, Yuejun Xue, Peng |
author_facet | Ren, Junjie Zhou, Jing Liu, Han Jiao, Xiaodan Cao, Yang Xu, Zhigang Kang, Yuejun Xue, Peng |
author_sort | Ren, Junjie |
collection | PubMed |
description | Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer. Methods: Mitochondrial-targeting liposomal nanoparticles (abbreviated MLipRIR NPs) are synthesized by the encapsulation of R162 (inhibitor of glutamate dehydrogenase 1 [GDH1]) and IR780 (a hydrophobic sonosensitizer) within the lipid bilayer, which are exploited for ultrasound (US)-activated tumor dyshomeostasis therapy reinforced by immunogenic cell death (ICD). Results: R162 released from MLipRIR NPs disrupts the glutaminolysis pathway in mitochondria, resulting in downregulated enzymatic activity of glutathione peroxidase (GPx). In addition, loaded IR780 can generate high levels of ROS under US irradiation, which not only interrupts mitochondrial respiration to induce apoptosis but also consumes local glutathione (GSH). GSH depletion accompanied by GPx deactivation causes severe ferroptosis of tumor cells through the accumulation of lipid peroxides. Such intracellular redox dyshomeostasis effectively triggers immunogenic cell death (ICD), which can activate antitumor immunity for the suppression of both primary and distant tumors with the aid of immune checkpoint blockade. Conclusions: Taking advantage of multimodal imaging for therapy guidance, this nanoplatform may potentiate systemic tumor eradication with high certainty. Taken together, this state-of-the-art paradigm may provide useful insights for cancer management by disrupting redox homeostasis. |
format | Online Article Text |
id | pubmed-8490505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-84905052021-10-12 Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem Ren, Junjie Zhou, Jing Liu, Han Jiao, Xiaodan Cao, Yang Xu, Zhigang Kang, Yuejun Xue, Peng Theranostics Research Paper Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer. Methods: Mitochondrial-targeting liposomal nanoparticles (abbreviated MLipRIR NPs) are synthesized by the encapsulation of R162 (inhibitor of glutamate dehydrogenase 1 [GDH1]) and IR780 (a hydrophobic sonosensitizer) within the lipid bilayer, which are exploited for ultrasound (US)-activated tumor dyshomeostasis therapy reinforced by immunogenic cell death (ICD). Results: R162 released from MLipRIR NPs disrupts the glutaminolysis pathway in mitochondria, resulting in downregulated enzymatic activity of glutathione peroxidase (GPx). In addition, loaded IR780 can generate high levels of ROS under US irradiation, which not only interrupts mitochondrial respiration to induce apoptosis but also consumes local glutathione (GSH). GSH depletion accompanied by GPx deactivation causes severe ferroptosis of tumor cells through the accumulation of lipid peroxides. Such intracellular redox dyshomeostasis effectively triggers immunogenic cell death (ICD), which can activate antitumor immunity for the suppression of both primary and distant tumors with the aid of immune checkpoint blockade. Conclusions: Taking advantage of multimodal imaging for therapy guidance, this nanoplatform may potentiate systemic tumor eradication with high certainty. Taken together, this state-of-the-art paradigm may provide useful insights for cancer management by disrupting redox homeostasis. Ivyspring International Publisher 2021-09-13 /pmc/articles/PMC8490505/ /pubmed/34646381 http://dx.doi.org/10.7150/thno.62984 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Ren, Junjie Zhou, Jing Liu, Han Jiao, Xiaodan Cao, Yang Xu, Zhigang Kang, Yuejun Xue, Peng Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title | Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title_full | Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title_fullStr | Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title_full_unstemmed | Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title_short | Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem |
title_sort | ultrasound (us)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (icd) through a mitochondrial targeting liposomal nanosystem |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490505/ https://www.ncbi.nlm.nih.gov/pubmed/34646381 http://dx.doi.org/10.7150/thno.62984 |
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