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Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy
Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of gluta...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415819/ https://www.ncbi.nlm.nih.gov/pubmed/32802183 http://dx.doi.org/10.7150/thno.46076 |
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author | Shen, Zijun Xia, Junfei Ma, Qingming Zhu, Wei Gao, Zhen Han, Shangcong Liang, Yan Cao, Jie Sun, Yong |
author_facet | Shen, Zijun Xia, Junfei Ma, Qingming Zhu, Wei Gao, Zhen Han, Shangcong Liang, Yan Cao, Jie Sun, Yong |
author_sort | Shen, Zijun |
collection | PubMed |
description | Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO(2)@Chitosan-CyI (MCC) for enhanced phototherapy. Methods: The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO(2) nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results: When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO(2) could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment. |
format | Online Article Text |
id | pubmed-7415819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-74158192020-08-13 Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy Shen, Zijun Xia, Junfei Ma, Qingming Zhu, Wei Gao, Zhen Han, Shangcong Liang, Yan Cao, Jie Sun, Yong Theranostics Research Paper Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO(2)@Chitosan-CyI (MCC) for enhanced phototherapy. Methods: The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO(2) nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results: When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO(2) could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment. Ivyspring International Publisher 2020-07-13 /pmc/articles/PMC7415819/ /pubmed/32802183 http://dx.doi.org/10.7150/thno.46076 Text en © The author(s) 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 Shen, Zijun Xia, Junfei Ma, Qingming Zhu, Wei Gao, Zhen Han, Shangcong Liang, Yan Cao, Jie Sun, Yong Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title | Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title_full | Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title_fullStr | Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title_full_unstemmed | Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title_short | Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy |
title_sort | tumor microenvironment-triggered nanosystems as dual-relief tumor hypoxia immunomodulators for enhanced phototherapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415819/ https://www.ncbi.nlm.nih.gov/pubmed/32802183 http://dx.doi.org/10.7150/thno.46076 |
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