Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism
Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the m...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25000052 |
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| author | Tianqi Nie Yifei Fang Ruhe Zhang Yishui Cai Xiaobo Wang Yuenong Jiao Jun Wu |
| author_facet | Tianqi Nie Yifei Fang Ruhe Zhang Yishui Cai Xiaobo Wang Yuenong Jiao Jun Wu |
| author_sort | Tianqi Nie |
| collection | DOAJ |
| description | Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability. Hence, in this article, a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor (acetazolamide, ACZ) and glucose oxidase (ACZ/GOx@SPM-HA Gel) was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid, along with ferrous coordination. Investigation on cancer cell lines (MOC-1) demonstrated ACZ/GOx@SPM-HA Gel may induce cellular oxidative stress and mitochondrial dysfunction through disrupting the cellular homeostasis. Moreover, with the facilitation of autophagy induced by spermidine, ACZ/GOx@SPM-HA Gel may trigger a positive feedback loop to maximally amplify cellular ferroptosis and promote DAMPs release. The anti-tumor evaluation on xenograft mice models furtherly proved the local injection of such hydrogel formulation could efficiently inhibit the tumor growth and distinctively promote the immunogenicity of tumor bed to provide a more favorable environment for immunotherapy. Overall, ACZ/GOx@SPM-HA Gel, with such feasible physiochemical properties and great biocompatibility, holds great potential in treating solid tumors with acidosis-mediated immunotherapy tolerance. |
| format | Article |
| id | doaj-art-c0bd9885b6874365835fc64a815c5ed1 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-c0bd9885b6874365835fc64a815c5ed12025-01-12T05:25:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-05-01475163Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanismTianqi Nie0Yifei Fang1Ruhe Zhang2Yishui Cai3Xiaobo Wang4Yuenong Jiao5Jun Wu6Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Twelfth People's Hospital (The Affiliated Twelfth People's Hospital of Guangzhou Medical University), Guangzhou Medical University, Guangzhou, 510620, ChinaBioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China; Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, ChinaDepartment of Hematology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518106, ChinaBioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, ChinaDepartment of Hematology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518106, China; Corresponding author. Department of Hematology, The Seventh Affiliated Hospital of Sun Yat-sen University, 628 Zhenyuan Road, Xinhu Street, Guangming, Shenzhen, 518106, China.Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Twelfth People's Hospital (The Affiliated Twelfth People's Hospital of Guangzhou Medical University), Guangzhou Medical University, Guangzhou, 510620, China; Corresponding author. Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Twelfth People's Hospital, Guangzhou, 510620, China.Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, 511400, China; Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China; Department of Hematology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518106, China; Corresponding author. Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), No.1 Du Xue Road, Nansha, Guangzhou, 511400, China.Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability. Hence, in this article, a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor (acetazolamide, ACZ) and glucose oxidase (ACZ/GOx@SPM-HA Gel) was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid, along with ferrous coordination. Investigation on cancer cell lines (MOC-1) demonstrated ACZ/GOx@SPM-HA Gel may induce cellular oxidative stress and mitochondrial dysfunction through disrupting the cellular homeostasis. Moreover, with the facilitation of autophagy induced by spermidine, ACZ/GOx@SPM-HA Gel may trigger a positive feedback loop to maximally amplify cellular ferroptosis and promote DAMPs release. The anti-tumor evaluation on xenograft mice models furtherly proved the local injection of such hydrogel formulation could efficiently inhibit the tumor growth and distinctively promote the immunogenicity of tumor bed to provide a more favorable environment for immunotherapy. Overall, ACZ/GOx@SPM-HA Gel, with such feasible physiochemical properties and great biocompatibility, holds great potential in treating solid tumors with acidosis-mediated immunotherapy tolerance.http://www.sciencedirect.com/science/article/pii/S2452199X25000052SpermidineTumor metabolic reprogrammingFerroptosisAutophagyCarbonic anhydrases |
| spellingShingle | Tianqi Nie Yifei Fang Ruhe Zhang Yishui Cai Xiaobo Wang Yuenong Jiao Jun Wu Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism Bioactive Materials Spermidine Tumor metabolic reprogramming Ferroptosis Autophagy Carbonic anhydrases |
| title | Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| title_full | Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| title_fullStr | Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| title_full_unstemmed | Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| title_short | Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| title_sort | self healable and ph responsive spermidine ferrous ion complexed hydrogel co loaded with ca inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism |
| topic | Spermidine Tumor metabolic reprogramming Ferroptosis Autophagy Carbonic anhydrases |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25000052 |
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