Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy
Abstract Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor ce...
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2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03599-1 |
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| author | Tao Jiang Zixiang Tang Shumiao Tian Haitian Tang Zhekun Jia Fangjian Li Chenyue Qiu Lin Deng Lang Ke Pan He Gang Liu Chengchao Chu Yongfu Xiong |
| author_facet | Tao Jiang Zixiang Tang Shumiao Tian Haitian Tang Zhekun Jia Fangjian Li Chenyue Qiu Lin Deng Lang Ke Pan He Gang Liu Chengchao Chu Yongfu Xiong |
| author_sort | Tao Jiang |
| collection | DOAJ |
| description | Abstract Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃]2⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe3⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe3⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe3⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical Abstract |
| format | Article |
| id | doaj-art-a5a7f36a4e3843d0ae8f57debd1b606a |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-a5a7f36a4e3843d0ae8f57debd1b606a2025-08-20T03:42:56ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123112010.1186/s12951-025-03599-1Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapyTao Jiang0Zixiang Tang1Shumiao Tian2Haitian Tang3Zhekun Jia4Fangjian Li5Chenyue Qiu6Lin Deng7Lang Ke8Pan He9Gang Liu10Chengchao Chu11Yongfu Xiong12Department of General Surgery, Academician (Expert) Workstation, Sichuan Digestive System Disease Clinical Medical Research Center, Affiliated Hospital of North Sichuan Medical CollegeDepartment of General Surgery, Academician (Expert) Workstation, Sichuan Digestive System Disease Clinical Medical Research Center, Affiliated Hospital of North Sichuan Medical CollegeXiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, School of Medicine, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityDepartment of General Surgery, Academician (Expert) Workstation, Sichuan Digestive System Disease Clinical Medical Research Center, Affiliated Hospital of North Sichuan Medical CollegeXiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Clinical Medicine, North Sichuan Medical CollegeXiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of ChinaState Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen UniversityXiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, School of Medicine, Xiamen UniversityDepartment of General Surgery, Academician (Expert) Workstation, Sichuan Digestive System Disease Clinical Medical Research Center, Affiliated Hospital of North Sichuan Medical CollegeAbstract Sonodynamic therapy (SDT) exhibits clinical potential for deep-tissue tumor treatment due to its deep tissue penetration and spatiotemporal controllability. Its core mechanism relies on ultrasound-activated sonosensitizers to generate reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. However, conventional sonosensitizers face limitations in ROS yield and tumor-targeting efficiency. In this study, we innovatively designed a multifunctional metal–organic nanosheet (TiZrRu-MON) by hydrothermal coordination of [Ru(bpy)₃]2⁺ photosensitizing units with TiZr-O clusters, while incorporating Fe3⁺ to construct a cascade catalytic system. Experimental results demonstrated that: (1) Fe3⁺ lattice doping significantly enhanced charge carrier mobility and ultrasound-triggered 1O₂ quantum yield via the formation charge transfer channels; (2) The acidic tumor microenvironment activated Fe3⁺-mediated Fenton reactions, establishing a positive feedback loop with SDT to synergistically amplify ROS generation; (3) Hyaluronic acid functionalization improved nanosheet internalization in HepG2 tumor cells through CD44 receptor-mediated endocytosis. Remarkably, ultrasound irradiation induced substantial oxidative stress and immunogenic cell death, promoting the release of damage-associated molecular patterns (DAMPs), which elevated the maturation rate of tumor-infiltrating dendritic cells (DCs) and significantly increased the proportion of CD8⁺ T cells. In a mouse subcutaneous tumor model, the system achieved effective tumor suppression with manageable systemic toxicity. This work proposes a metal–ligand coordination strategy to advance the development of high-performance sonosensitizers and immunomodulatory antitumor technologies. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03599-1Metal–organic nanostructureSonodynamic therapyChemodynamic therapyMagnetic resonance imagingCancer therapy |
| spellingShingle | Tao Jiang Zixiang Tang Shumiao Tian Haitian Tang Zhekun Jia Fangjian Li Chenyue Qiu Lin Deng Lang Ke Pan He Gang Liu Chengchao Chu Yongfu Xiong Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy Journal of Nanobiotechnology Metal–organic nanostructure Sonodynamic therapy Chemodynamic therapy Magnetic resonance imaging Cancer therapy |
| title | Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy |
| title_full | Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy |
| title_fullStr | Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy |
| title_full_unstemmed | Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy |
| title_short | Metal–organic nanostructures based on sono/chemo-nanodynamic synergy of TixOy/Ru reaction units: for ultrasound-induced dynamic cancer therapy |
| title_sort | metal organic nanostructures based on sono chemo nanodynamic synergy of tixoy ru reaction units for ultrasound induced dynamic cancer therapy |
| topic | Metal–organic nanostructure Sonodynamic therapy Chemodynamic therapy Magnetic resonance imaging Cancer therapy |
| url | https://doi.org/10.1186/s12951-025-03599-1 |
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