Ascorbic Acid-Derived Supramolecular Gels Induce Immunogenic Ferroptosis in Cancer Cells to Potentiate Tumor Immunotherapy
文献类型：期刊论文
| 作者 | Cai, Wenjiao2,3; Sun, Yuelan2,3; Xu, Wenyue1,2; Kuang, Xiuru2,3; Zhang, Zhe2; Cao, Xiang2; Xu, Junyu2; Li, Yi2; Huang, Yongzhuo1,2,3; Shen, Shiyang1,2,3 |
| 刊名 | ACS NANO
 |
| 出版日期 | 2025-09-16 |
| 卷号 | 19期号:36页码:32405-32421 |
| 关键词 | ascorbic acid supramolecular gels ferroptosis immunogenic cell death tumor immunotherapy |
| ISSN号 | 1936-0851 |
| DOI | 10.1021/acsnano.5c08353 |
| 通讯作者 | Huang, Yongzhuo(yzhuang@simm.ac.cn) ; Shen, Shiyang(shenshiyang@simm.ac.cn) |
| 英文摘要 | High-dose ascorbic acid (AA) therapy induces cancer cell death primarily through its oxidized derivative, dehydroascorbic acid (DHA). However, maintaining therapeutic AA concentrations within tumors and overcoming intratumoral hypoxia pose critical barriers to the clinical application of AA. Herein, we develop an injectable supramolecular gel (alpha PD-1@Lv/HPAGel) composed of ascorbyl palmitate (an AA derivative), lovastatin-loaded hemoglobin nanoparticles (Lv/Hb-PDA), and the immune checkpoint inhibitor anti-PD-1 (alpha PD-1). Upon intratumoral administration, this gel system sustains high local AA concentrations and promotes efficient oxidation of AA into DHA by alleviating hypoxia via the release of oxygen from hemoglobin. Simultaneously, lovastatin inhibits glutathione peroxidase 4, synergistically amplifying AA-induced ferroptosis. The coordinated induction of ferroptosis remodels the tumor immune microenvironment and stimulates a robust antitumor immune response. In combination with alpha PD-1, the gel system suppresses tumor growth and metastasis, establishes durable immune memory, and effectively prevents local and distant tumor recurrence postsurgery. Collectively, these findings present an approach for translating high-dose AA therapy into practice and provide evidence for the integration of ferroptosis induction with immunotherapy for enhanced cancer treatment. |
| WOS关键词 | VITAMIN-C |
| 资助项目 | National Natural Science Foundation of China[82104090] ; National Natural Science Foundation of China[2025A1515010594] ; Guangdong Basic and Applied Basic Research Foundation, China[2024B2016] ; Social Public Welfare and Basic Research Project of Zhongshan City, China[CXTD2024007] ; Innovative Scientific Research Team Project of Zhongshan City, China[DSQZ-QN-202302] ; National Key Laboratory of Advanced Drug Delivery and Release Systems, China[2019B090904008] ; Project of High-level New R&D Institute, Department of Science and Technology of Guangdong Province, China[2021B0909050003] ; High-level Innovative Research Institute, Department of Science and Technology of Guangdong Province, China |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001561602000001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321372]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, Yongzhuo; Shen, Shiyang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Pharmaceut Preparat Res Ctr, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 3.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cai, Wenjiao,Sun, Yuelan,Xu, Wenyue,et al. Ascorbic Acid-Derived Supramolecular Gels Induce Immunogenic Ferroptosis in Cancer Cells to Potentiate Tumor Immunotherapy[J]. ACS NANO,2025,19(36):32405-32421. |
| APA | Cai, Wenjiao.,Sun, Yuelan.,Xu, Wenyue.,Kuang, Xiuru.,Zhang, Zhe.,...&Shen, Shiyang.(2025).Ascorbic Acid-Derived Supramolecular Gels Induce Immunogenic Ferroptosis in Cancer Cells to Potentiate Tumor Immunotherapy.ACS NANO,19(36),32405-32421. |
| MLA | Cai, Wenjiao,et al."Ascorbic Acid-Derived Supramolecular Gels Induce Immunogenic Ferroptosis in Cancer Cells to Potentiate Tumor Immunotherapy".ACS NANO 19.36(2025):32405-32421. |
入库方式： OAI收割
来源：上海药物研究所
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