Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy
Advanced drug delivery systems integrating immunomodulatory functions can improve cancer therapy. Herein, we develop a novel metal-phenolic capsule for synergistic drug delivery and immunomodulation. Specifically, a stable metal-phenolic network (MPN), formed by Fe (III), tannic acid, and catechol-m...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2025-01-01
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| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0752 |
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| author | Xin Tan Xiaojing Wu Renwang Sheng Yinghua Tao Weikun Li Yanling Liang Bo Gui Huiqin Lu Diyi Feng Nuoya Chen Fangzhou Liu Ling Liu Liqin Ge |
| author_facet | Xin Tan Xiaojing Wu Renwang Sheng Yinghua Tao Weikun Li Yanling Liang Bo Gui Huiqin Lu Diyi Feng Nuoya Chen Fangzhou Liu Ling Liu Liqin Ge |
| author_sort | Xin Tan |
| collection | DOAJ |
| description | Advanced drug delivery systems integrating immunomodulatory functions can improve cancer therapy. Herein, we develop a novel metal-phenolic capsule for synergistic drug delivery and immunomodulation. Specifically, a stable metal-phenolic network (MPN), formed by Fe (III), tannic acid, and catechol-modified hyaluronic acid, was assembled onto doxorubicin (DOX)-loaded mannose-glycated bovine serum albumin microbubbles to construct microcapsules with both drug loading and immunomodulatory functions simultaneously. The capsules release DOX in a pH-responsive manner and induce reactive oxygen species accumulation in tumor cells, thereby enhancing immunogenic cell death (ICD). This ICD effect, combined with the direct stimulation of dendritic cells (DCs) by the capsules and the paracrine signaling from capsule-activated M1 macrophages, synergistically promotes DC maturation. In vivo bilateral tumor models demonstrate that DmTFH substantially inhibits primary and distant tumor development and markedly delays metastasis to the lungs. Flow cytometry analysis confirms robust local and systemic immune responses, characterized by enhanced DC maturation within lymph nodes and increased infiltration of activated CD8+ and CD4+ T cells in tumors and spleens. Overall, the immunoactive MPN microcapsules constructed in this study enhance the immunotherapeutic efficacy of DOX through the synergistic action of carrier-inherent immunomodulation and chemotherapy, providing a promising approach for combinatorial cancer therapy. |
| format | Article |
| id | doaj-art-ca929f2440fe45de96359a18a40fdfbc |
| institution | DOAJ |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-ca929f2440fe45de96359a18a40fdfbc2025-08-20T03:15:39ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0752Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer ImmunotherapyXin Tan0Xiaojing Wu1Renwang Sheng2Yinghua Tao3Weikun Li4Yanling Liang5Bo Gui6Huiqin Lu7Diyi Feng8Nuoya Chen9Fangzhou Liu10Ling Liu11Liqin Ge12State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, P.R. China.School of Medicine, Southeast University, Nanjing 210009, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.Department of Head & Neck Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.Department of Head & Neck Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing 210029, P.R. China.Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, P.R. China.State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P.R. China.Advanced drug delivery systems integrating immunomodulatory functions can improve cancer therapy. Herein, we develop a novel metal-phenolic capsule for synergistic drug delivery and immunomodulation. Specifically, a stable metal-phenolic network (MPN), formed by Fe (III), tannic acid, and catechol-modified hyaluronic acid, was assembled onto doxorubicin (DOX)-loaded mannose-glycated bovine serum albumin microbubbles to construct microcapsules with both drug loading and immunomodulatory functions simultaneously. The capsules release DOX in a pH-responsive manner and induce reactive oxygen species accumulation in tumor cells, thereby enhancing immunogenic cell death (ICD). This ICD effect, combined with the direct stimulation of dendritic cells (DCs) by the capsules and the paracrine signaling from capsule-activated M1 macrophages, synergistically promotes DC maturation. In vivo bilateral tumor models demonstrate that DmTFH substantially inhibits primary and distant tumor development and markedly delays metastasis to the lungs. Flow cytometry analysis confirms robust local and systemic immune responses, characterized by enhanced DC maturation within lymph nodes and increased infiltration of activated CD8+ and CD4+ T cells in tumors and spleens. Overall, the immunoactive MPN microcapsules constructed in this study enhance the immunotherapeutic efficacy of DOX through the synergistic action of carrier-inherent immunomodulation and chemotherapy, providing a promising approach for combinatorial cancer therapy.https://spj.science.org/doi/10.34133/research.0752 |
| spellingShingle | Xin Tan Xiaojing Wu Renwang Sheng Yinghua Tao Weikun Li Yanling Liang Bo Gui Huiqin Lu Diyi Feng Nuoya Chen Fangzhou Liu Ling Liu Liqin Ge Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy Research |
| title | Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy |
| title_full | Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy |
| title_fullStr | Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy |
| title_full_unstemmed | Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy |
| title_short | Microbubble-Templated Immunoactive Metal-Phenolic Capsules for Drug Delivery and Enhanced Cancer Immunotherapy |
| title_sort | microbubble templated immunoactive metal phenolic capsules for drug delivery and enhanced cancer immunotherapy |
| url | https://spj.science.org/doi/10.34133/research.0752 |
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