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Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor
BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686264/ https://www.ncbi.nlm.nih.gov/pubmed/34930284 http://dx.doi.org/10.1186/s12951-021-01196-6 |
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author | Wen, Jiexin Luo, Yong Gao, Hui Zhang, Liang Wang, Xiang Huang, Ju Shang, Tingting Zhou, Di Wang, Dong Wang, Zhigang Li, Pan Wang, Zhaoxia |
author_facet | Wen, Jiexin Luo, Yong Gao, Hui Zhang, Liang Wang, Xiang Huang, Ju Shang, Tingting Zhou, Di Wang, Dong Wang, Zhigang Li, Pan Wang, Zhaoxia |
author_sort | Wen, Jiexin |
collection | PubMed |
description | BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01196-6. |
format | Online Article Text |
id | pubmed-8686264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86862642021-12-20 Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor Wen, Jiexin Luo, Yong Gao, Hui Zhang, Liang Wang, Xiang Huang, Ju Shang, Tingting Zhou, Di Wang, Dong Wang, Zhigang Li, Pan Wang, Zhaoxia J Nanobiotechnology Research BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01196-6. BioMed Central 2021-12-20 /pmc/articles/PMC8686264/ /pubmed/34930284 http://dx.doi.org/10.1186/s12951-021-01196-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wen, Jiexin Luo, Yong Gao, Hui Zhang, Liang Wang, Xiang Huang, Ju Shang, Tingting Zhou, Di Wang, Dong Wang, Zhigang Li, Pan Wang, Zhaoxia Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title | Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title_full | Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title_fullStr | Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title_full_unstemmed | Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title_short | Mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
title_sort | mitochondria-targeted nanoplatforms for enhanced photodynamic therapy against hypoxia tumor |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686264/ https://www.ncbi.nlm.nih.gov/pubmed/34930284 http://dx.doi.org/10.1186/s12951-021-01196-6 |
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