Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy
文献类型：期刊论文
| 作者 | Wang, Rui7,8; Song, Wenqin6; Zhu, Jie5,7; Shao, Xinyue5,7; Yang, Chenxiao7,8; Xiong, Wei4; Wang, Bing7; Zhao, Pengfei3; Chen, Meiwan2; Huang, Yongzhuo1,4,5,6,7
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| 刊名 | JOURNAL OF CONTROLLED RELEASE
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| 出版日期 | 2024-04-01 |
| 卷号 | 368页码:84-96 |
| 关键词 | Anti-glioma Diethyldithiocarbamate Cu/Fe Immunogenic cell death Ferroptosis Metalloimmunology Albumin Lactoferrin Brain-targeted delivery |
| ISSN号 | 0168-3659 |
| DOI | 10.1016/j.jconrel.2024.02.004 |
| 通讯作者 | Zhao, Pengfei(zhaopf0507@zju.edu.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn) |
| 英文摘要 | Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc(-)) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment. |
| WOS关键词 | TUMOR MICROENVIRONMENT ; CELL-DEATH ; CANCER ; TRANSCYTOSIS ; TEMOZOLOMIDE ; BEVACIZUMAB ; TARGETS ; ALBUMIN |
| 资助项目 | National Key Research and Development Program of China[2021YFE0103100] ; National Key Research and Development Program of China[2021YFC2400600] ; National Key Research and Development Program of China[2022YFE0203600] ; National Natural Science Foundation of China[82204282] ; National Natural Science Foundation of China[81925035] ; National Natural Science Foundation of China[82341232] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2019B090904008] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001202974100001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/310759]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhao, Pengfei; Huang, Yongzhuo |
| 作者单位 | 1.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China 2.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China 3.Zhejiang Univ, Affiliated Hosp 2, Ctr Clin Pharmacol, Sch Med, Hangzhou 310009, Peoples R China 4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Nanchang Univ, Jiangxi Med Coll, Sch Pharm, Nanchang 330006, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Rui,Song, Wenqin,Zhu, Jie,et al. Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy[J]. JOURNAL OF CONTROLLED RELEASE,2024,368:84-96. |
| APA | Wang, Rui.,Song, Wenqin.,Zhu, Jie.,Shao, Xinyue.,Yang, Chenxiao.,...&Huang, Yongzhuo.(2024).Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy.JOURNAL OF CONTROLLED RELEASE,368,84-96. |
| MLA | Wang, Rui,et al."Biomimetic nano-chelate diethyldithiocarbamate Cu/Fe for enhanced metalloimmunity and ferroptosis activation in glioma therapy".JOURNAL OF CONTROLLED RELEASE 368(2024):84-96. |
入库方式： OAI收割
来源：上海药物研究所
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