Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic...

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Main Authors: Jing Li, Yu Wang, Jun Tao, Xiaodan Su, Feipeng Zhu, Wei Lu, Xiaolin Han, Meng Dang, Lixing Weng
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Bioinorganic Chemistry and Applications
Online Access:http://dx.doi.org/10.1155/2024/6618388
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author Jing Li
Yu Wang
Jun Tao
Xiaodan Su
Feipeng Zhu
Wei Lu
Xiaolin Han
Meng Dang
Lixing Weng
author_facet Jing Li
Yu Wang
Jun Tao
Xiaodan Su
Feipeng Zhu
Wei Lu
Xiaolin Han
Meng Dang
Lixing Weng
author_sort Jing Li
collection DOAJ
description Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.
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spelling doaj-art-eedf0a5e0eab41c38ab4db48c9a5f0132025-02-03T01:29:31ZengWileyBioinorganic Chemistry and Applications1687-479X2024-01-01202410.1155/2024/6618388Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic TherapyJing Li0Yu Wang1Jun Tao2Xiaodan Su3Feipeng Zhu4Wei Lu5Xiaolin Han6Meng Dang7Lixing Weng8Key Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsDepartment of RadiologyKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsKey Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for BiosensorsCollege of Geography and Biological InformationPhotodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.http://dx.doi.org/10.1155/2024/6618388
spellingShingle Jing Li
Yu Wang
Jun Tao
Xiaodan Su
Feipeng Zhu
Wei Lu
Xiaolin Han
Meng Dang
Lixing Weng
Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
Bioinorganic Chemistry and Applications
title Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
title_full Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
title_fullStr Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
title_full_unstemmed Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
title_short Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy
title_sort mitochondria targeting and oxygen self supplying eccentric hollow nanoplatform for enhanced breast cancer photodynamic therapy
url http://dx.doi.org/10.1155/2024/6618388
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