Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors
Abstract Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensiti...
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03116-4 |
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| author | Song Li Yunheng Liu Xiaokang Zhang Yurong Liu Longqing Si Shaojing Jiang Aoya Wang Xukai Che Jing Chen Jinghui Hu |
| author_facet | Song Li Yunheng Liu Xiaokang Zhang Yurong Liu Longqing Si Shaojing Jiang Aoya Wang Xukai Che Jing Chen Jinghui Hu |
| author_sort | Song Li |
| collection | DOAJ |
| description | Abstract Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe3+, which is reduced to Fe2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy. |
| format | Article |
| id | doaj-art-fe575586263543afa7f5557107f5a0d9 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-fe575586263543afa7f5557107f5a0d92025-01-26T12:50:53ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123111810.1186/s12951-025-03116-4Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumorsSong Li0Yunheng Liu1Xiaokang Zhang2Yurong Liu3Longqing Si4Shaojing Jiang5Aoya Wang6Xukai Che7Jing Chen8Jinghui Hu9School of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversityYantai Engineering Research Center for Digital Technology of Stomatology, School of Stomatology, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversitySchool of Pharmacy, Binzhou Medical UniversityYantai Engineering Research Center for Digital Technology of Stomatology, School of Stomatology, Binzhou Medical UniversityAbstract Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe3+, which is reduced to Fe2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy.https://doi.org/10.1186/s12951-025-03116-4PhotoimmunotherapyDihydroartemisininIR-780TransferrinReactive oxygen species |
| spellingShingle | Song Li Yunheng Liu Xiaokang Zhang Yurong Liu Longqing Si Shaojing Jiang Aoya Wang Xukai Che Jing Chen Jinghui Hu Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors Journal of Nanobiotechnology Photoimmunotherapy Dihydroartemisinin IR-780 Transferrin Reactive oxygen species |
| title | Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| title_full | Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| title_fullStr | Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| title_full_unstemmed | Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| title_short | Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| title_sort | multi pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors |
| topic | Photoimmunotherapy Dihydroartemisinin IR-780 Transferrin Reactive oxygen species |
| url | https://doi.org/10.1186/s12951-025-03116-4 |
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