Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma
Abstract Achieving bone defect repair while preventing tumor recurrence after osteosarcoma surgery has consistently posed a clinical challenge. Local treatment with 3D-printed scaffolds loaded with chemotherapeutic drugs can exert certain effects in tumor inhibition and bone regeneration. However, t...
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BMC
2025-04-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03253-w |
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| author | Zuyun Yan Youwen Deng Liping Huang Jin Zeng Dong Wang Zhaochen Tong Qizhi Fan Wei Tan Jinpeng Yan Xiaofang Zang Shijie Chen |
| author_facet | Zuyun Yan Youwen Deng Liping Huang Jin Zeng Dong Wang Zhaochen Tong Qizhi Fan Wei Tan Jinpeng Yan Xiaofang Zang Shijie Chen |
| author_sort | Zuyun Yan |
| collection | DOAJ |
| description | Abstract Achieving bone defect repair while preventing tumor recurrence after osteosarcoma surgery has consistently posed a clinical challenge. Local treatment with 3D-printed scaffolds loaded with chemotherapeutic drugs can exert certain effects in tumor inhibition and bone regeneration. However, the non-specific activation of chemotherapeutic drugs leads to high local toxic side effects and the formation of an immunosuppressive tumor microenvironment, thereby limiting their clinical application and therapeutic efficacy. To address this, we designed a Pt (IV) prodrug with low toxicity and minimal side effects, which releases Pt (II) in response to glutathione. This prodrug was grafted onto polydopamine (PDA) through an amidation reaction, resulting in a composite nanomaterial (PDA@Pt) that possesses both photothermal synergistic chemotherapy and immuno-oncological properties. Subsequently, we innovatively employed selective laser sintering technology to incorporate PDA@Pt into a poly (L-lactic acid)/bioactive glass matrix, successfully constructing a composite scaffold with dual anti-tumor and bone repair capabilities. The study revealed that the composite scaffold significantly inhibited the growth of osteosarcoma cells and activated the cGAS-STING pathway by inducing DNA damage, ultimately converting the ‘cold tumor’ into a ‘hot tumor.’ Additionally, the composite scaffold could induce osteogenic differentiation of bone marrow mesenchymal stem cells and exhibited excellent bone repair capabilities in vivo. Graphical abstract |
| format | Article |
| id | doaj-art-c42ea6506b1f4baf8c7b524df3b9546d |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-c42ea6506b1f4baf8c7b524df3b9546d2025-08-20T03:10:13ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123112010.1186/s12951-025-03253-wBiopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcomaZuyun Yan0Youwen Deng1Liping Huang2Jin Zeng3Dong Wang4Zhaochen Tong5Qizhi Fan6Wei Tan7Jinpeng Yan8Xiaofang Zang9Shijie Chen10Department of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Cell Biology, School of Life Sciences, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityDepartment of Spine Surgery, The Third Xiangya Hospital, Central South UniversityAbstract Achieving bone defect repair while preventing tumor recurrence after osteosarcoma surgery has consistently posed a clinical challenge. Local treatment with 3D-printed scaffolds loaded with chemotherapeutic drugs can exert certain effects in tumor inhibition and bone regeneration. However, the non-specific activation of chemotherapeutic drugs leads to high local toxic side effects and the formation of an immunosuppressive tumor microenvironment, thereby limiting their clinical application and therapeutic efficacy. To address this, we designed a Pt (IV) prodrug with low toxicity and minimal side effects, which releases Pt (II) in response to glutathione. This prodrug was grafted onto polydopamine (PDA) through an amidation reaction, resulting in a composite nanomaterial (PDA@Pt) that possesses both photothermal synergistic chemotherapy and immuno-oncological properties. Subsequently, we innovatively employed selective laser sintering technology to incorporate PDA@Pt into a poly (L-lactic acid)/bioactive glass matrix, successfully constructing a composite scaffold with dual anti-tumor and bone repair capabilities. The study revealed that the composite scaffold significantly inhibited the growth of osteosarcoma cells and activated the cGAS-STING pathway by inducing DNA damage, ultimately converting the ‘cold tumor’ into a ‘hot tumor.’ Additionally, the composite scaffold could induce osteogenic differentiation of bone marrow mesenchymal stem cells and exhibited excellent bone repair capabilities in vivo. Graphical abstracthttps://doi.org/10.1186/s12951-025-03253-wAntitumourPt (IV) prodrugsPhotothermal therapyImmunityBone regeneration |
| spellingShingle | Zuyun Yan Youwen Deng Liping Huang Jin Zeng Dong Wang Zhaochen Tong Qizhi Fan Wei Tan Jinpeng Yan Xiaofang Zang Shijie Chen Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma Journal of Nanobiotechnology Antitumour Pt (IV) prodrugs Photothermal therapy Immunity Bone regeneration |
| title | Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma |
| title_full | Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma |
| title_fullStr | Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma |
| title_full_unstemmed | Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma |
| title_short | Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma |
| title_sort | biopolymer based bone scaffold for controlled pt iv prodrug release and synergistic photothermal chemotherapy and immunotherapy in osteosarcoma |
| topic | Antitumour Pt (IV) prodrugs Photothermal therapy Immunity Bone regeneration |
| url | https://doi.org/10.1186/s12951-025-03253-w |
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