In-situ trichosanthin-IL2/pectin dynamic hydrogel activates dendritic cells and reverses T cell exhaustion for post-operative cancer therapy
文献类型：期刊论文
| 作者 | Gu, Zeyun7,8,9; Chen, Guihua6; Gao, Nan4,5; Yao, Shuo3; Zhang, Xiaoru6; Xu, Quangang7; Xiong, Wei6; Liu, Lin7; Liu, Qin6; Yin, Dan8,9 |
| 刊名 | CHEMICAL ENGINEERING JOURNAL
 |
| 出版日期 | 2025-02-01 |
| 卷号 | 505页码:12 |
| 关键词 | Trichosanthin IL2 Hydrogel Postoperative administration Cancer immunotherapy Dendritic cells |
| ISSN号 | 1385-8947 |
| DOI | 10.1016/j.cej.2025.159426 |
| 英文摘要 | Postoperative recurrence and metastasis of triple-negative breast cancer (TNBC) remain major clinical challenges due to immunosuppression and poor immune recognition of residual cancer cells. Here, we present a novel polysaccharide-protein hydrogel implant, composed of a trichosanthin (TCS)-IL2 fusion protein crosslinked with oxidized pectin, designed for sustained local immunotherapy following tumor resection. TCS is a plant-derived protein with immune-stimulatory properties. This in-situ forming gel (termed TL-pectin gel) delivers the TCS-IL2 (TL) protein to enhance dendritic cell (DC) maturation, improve antigen presentation, and reverse T-cell exhaustion, thereby stimulating tumor-specific cytotoxicity. In a mouse breast cancer model, the TL-pectin hydrogel effectively inhibited local tumor recurrence and reduced lung and brain metastases, demonstrating its potential to improve postoperative outcomes. Mechanistic studies indicated that TCS activated the NF-kappa B pathway, enhanced cytokine secretion and CD8+ T-cell differentiation, and IL2 maintained T-cell proliferation and activity. The hydrogel showed excellent biocompatibility and functioned as a controlled-release system to form a localized immunostimulatory microenvironment. This study suggests that TL-pectin gel is a promising candidate for clinical translation, offering a potential approach for adjuvant cancer immunotherapy. |
| 资助项目 | National Key Research and Development Program of China, China[2021YFC2400600] ; National Key Research and Development Program of China, China[2022YFE0203600] ; NFSC[81925035] ; NFSC[82341232] ; Department of Science and Technology of Guangdong Province[2019B090904008] ; Department of Science and Technology of Guangdong Province[2021B0909050003] ; Chinese Academy of Sciences President's International Fellowship Initiative[2024VBB0004] ; Scientific Innovation Group Project in Zhongshan[LJ2021001] |
| WOS研究方向 | Engineering |
| 语种 | 英语 |
| WOS记录号 | WOS:001401944600001 |
| 出版者 | ELSEVIER SCIENCE SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315917]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zhu, Xiao-Ming; Huang, Yongzhuo |
| 作者单位 | 1.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Guangdong Pharmaceut Univ, Guangzhou, Peoples R China 4.Macau Univ Sci & Technol, Fac Med, Sch Pharm, Taipa 999078, Macao, Peoples R China 5.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China 6.Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangdong Clin Res Acad Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China 7.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China 8.Macau Univ Sci & Technol, Fac Chinese Med, Taipa 999078, Macao, Peoples R China 9.Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gu, Zeyun,Chen, Guihua,Gao, Nan,et al. In-situ trichosanthin-IL2/pectin dynamic hydrogel activates dendritic cells and reverses T cell exhaustion for post-operative cancer therapy[J]. CHEMICAL ENGINEERING JOURNAL,2025,505:12. |
| APA | Gu, Zeyun.,Chen, Guihua.,Gao, Nan.,Yao, Shuo.,Zhang, Xiaoru.,...&Huang, Yongzhuo.(2025).In-situ trichosanthin-IL2/pectin dynamic hydrogel activates dendritic cells and reverses T cell exhaustion for post-operative cancer therapy.CHEMICAL ENGINEERING JOURNAL,505,12. |
| MLA | Gu, Zeyun,et al."In-situ trichosanthin-IL2/pectin dynamic hydrogel activates dendritic cells and reverses T cell exhaustion for post-operative cancer therapy".CHEMICAL ENGINEERING JOURNAL 505(2025):12. |
入库方式： OAI收割
来源：上海药物研究所
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