Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors
Tumor microenvironment (TME), as the “soil” of tumor growth and metastasis, exhibits significant differences from normal physiological conditions. However, how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge. Herein, an innovative...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2024-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X23004310 |
| _version_ | 1797324330705616896 |
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| author | Jie Liu Tianfeng Yang Handan Zhang Lin Weng Xiuhong Peng Tao Liu Cheng Cheng Yanmin Zhang Xin Chen |
| author_facet | Jie Liu Tianfeng Yang Handan Zhang Lin Weng Xiuhong Peng Tao Liu Cheng Cheng Yanmin Zhang Xin Chen |
| author_sort | Jie Liu |
| collection | DOAJ |
| description | Tumor microenvironment (TME), as the “soil” of tumor growth and metastasis, exhibits significant differences from normal physiological conditions. However, how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge. Herein, an innovative nanoreactor (AH@MBTF) is developed to utilize the apparent differences (copper concentration and H2O2 level) between tumor cells and normal cells to eliminate primary tumor based on H2O2-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation. This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea (BTU), triphenylphosphine (TPP), and folic acid (FA), while being co-loaded with horseradish peroxidase (HRP) and its substrate ABTS. During therapy, the BTU moieties on AH@MBTF could capture excessive copper (highly correlated with tumor metastasis), presenting exceptional anti-metastasis activity. Simultaneously, the complexation between BTU and copper triggers the formation of cuprous ions, which further react with H2O2 to generate cytotoxic hydroxyl radical (•OH), inhibiting tumor growth via chemodynamic therapy. Additionally, the stepwise targeting of FA and TPP guides AH@MBTF to accurately accumulate in tumor mitochondria, containing abnormally high levels of H2O2. As a catalyst, HRP mediates the oxidation reaction between ABTS and H2O2 to yield activated ABTS•+. Upon 808 nm laser irradiation, the activated ABTS•+ performs tumor-specific photothermal therapy, achieving the ablation of primary tumor by raising the tissue temperature. Collectively, this intelligent nanoreactor possesses profound potential in inhibiting tumor progression and metastasis. |
| first_indexed | 2024-03-08T05:54:35Z |
| format | Article |
| id | doaj.art-521dfa4b493e472e8d459578ab85f877 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-03-08T05:54:35Z |
| publishDate | 2024-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-521dfa4b493e472e8d459578ab85f8772024-02-05T04:32:04ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-04-0134354365Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumorsJie Liu0Tianfeng Yang1Handan Zhang2Lin Weng3Xiuhong Peng4Tao Liu5Cheng Cheng6Yanmin Zhang7Xin Chen8School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiaotong University, Xi’an, 710049, ChinaSchool of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, ChinaSchool of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiaotong University, Xi’an, 710049, ChinaSchool of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiaotong University, Xi’an, 710049, ChinaSchool of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, ChinaSchool of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiaotong University, Xi’an, 710049, ChinaSchool of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, ChinaSchool of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, China; Corresponding author.School of Chemical Engineering and Technology, Shaanxi Key Laboratory of Energy Chemical Process Intensification, Institute of Polymer Science in Chemical Engineering, Xi’an Jiaotong University, Xi’an, 710049, China; Corresponding author.Tumor microenvironment (TME), as the “soil” of tumor growth and metastasis, exhibits significant differences from normal physiological conditions. However, how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a challenge. Herein, an innovative nanoreactor (AH@MBTF) is developed to utilize the apparent differences (copper concentration and H2O2 level) between tumor cells and normal cells to eliminate primary tumor based on H2O2-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper complexation. This nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea (BTU), triphenylphosphine (TPP), and folic acid (FA), while being co-loaded with horseradish peroxidase (HRP) and its substrate ABTS. During therapy, the BTU moieties on AH@MBTF could capture excessive copper (highly correlated with tumor metastasis), presenting exceptional anti-metastasis activity. Simultaneously, the complexation between BTU and copper triggers the formation of cuprous ions, which further react with H2O2 to generate cytotoxic hydroxyl radical (•OH), inhibiting tumor growth via chemodynamic therapy. Additionally, the stepwise targeting of FA and TPP guides AH@MBTF to accurately accumulate in tumor mitochondria, containing abnormally high levels of H2O2. As a catalyst, HRP mediates the oxidation reaction between ABTS and H2O2 to yield activated ABTS•+. Upon 808 nm laser irradiation, the activated ABTS•+ performs tumor-specific photothermal therapy, achieving the ablation of primary tumor by raising the tissue temperature. Collectively, this intelligent nanoreactor possesses profound potential in inhibiting tumor progression and metastasis.http://www.sciencedirect.com/science/article/pii/S2452199X23004310NanoreactorH2O2-dependentPhotothermal-chemodynamic therapyCopper depletionTumor metastasis inhibition |
| spellingShingle | Jie Liu Tianfeng Yang Handan Zhang Lin Weng Xiuhong Peng Tao Liu Cheng Cheng Yanmin Zhang Xin Chen Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors Bioactive Materials Nanoreactor H2O2-dependent Photothermal-chemodynamic therapy Copper depletion Tumor metastasis inhibition |
| title | Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| title_full | Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| title_fullStr | Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| title_full_unstemmed | Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| title_short | Intelligent nanoreactor coupling tumor microenvironment manipulation and H2O2-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| title_sort | intelligent nanoreactor coupling tumor microenvironment manipulation and h2o2 dependent photothermal chemodynamic therapy for accurate treatment of primary and metastatic tumors |
| topic | Nanoreactor H2O2-dependent Photothermal-chemodynamic therapy Copper depletion Tumor metastasis inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X23004310 |
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