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Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer

文献类型：期刊论文

作者Zheng, Chao1,5,6,7,8; Jiang, Linyang4,6,7; Gong, Xiang5,6,7; Zhang, Wen5,6,7; Pu, Rong3,6,7; Zhang, Yuan2; Zhao, Mengmeng2; Jiang, Chen1,8; Wang, Hao1,5,8; Zhang, Pengcheng11,12,13
刊名JOURNAL OF CONTROLLED RELEASE
出版日期2024-12-01
卷号376页码:138-148
关键词Synthetic high-density lipoprotein Cabozantinib Maytansine Myeloid-derived suppressor cell Immunosuppression Colorectal cancer
ISSN号0168-3659
DOI10.1016/j.jconrel.2024.09.047
英文摘要Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein (ECCD-sHDL) to modulate the tumor microenvironment. DM1 induced immunogenic cell death and promoted the maturation of dendritic cells. Meanwhile, Cabo alleviated DM1-induced succinate release, preventing tuft cell activation, downregulating IL-25 and IL-13 secretion, and reducing intratumoral MDSC infiltration. ECCD-sHDL increased the densities of active cytotoxic T lymphocytes (CTLs) and M1 macrophages in the tumors, effectively inhibiting tumor growth and metastasis, thereby prolonging survival in murine CRC models. Our study sheds light on the mechanism of treatmentinduced immunosuppression in orthotopic CRC and demonstrates that this combinatorial therapy could be an effective treatment for CRC.
WOS关键词IMMUNE ; COLITIS
资助项目National Key Research and Development Program of China[2022YFC3401400] ; National Natural Science Foundation of China[32171374] ; National Natural Science Foundation of China[32371457] ; National Natural Science Foundation of China[82270064] ; National Natural Science Foundation of China[82100073] ; Shandong Provincial Natural Science Foundation[ZR2019ZD25] ; Shandong Laboratory Program[SYS202205]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS记录号WOS:001347568600001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/314321]  
专题新药研究国家重点实验室
通讯作者Jiang, Chen; Wang, Hao; Zhang, Pengcheng; Li, Yaping
作者单位1.MOE Frontiers Ctr Brain Sci, Shanghai 201203, Peoples R China
2.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pulm & Crit Care Med, Shanghai 200433, Peoples R China
3.Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.China State Inst Pharmaceut Ind, Natl Adv Med Engn Res Ctr, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
8.Fudan Univ, Sch Pharm, State Key Lab Med Neurobiol, Key Lab Smart Drug Delivery,Minist Educ,Dept Pharm, Shanghai 201203, Peoples R China
9.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
10.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Chao,Jiang, Linyang,Gong, Xiang,et al. Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer[J]. JOURNAL OF CONTROLLED RELEASE,2024,376:138-148.
APA Zheng, Chao.,Jiang, Linyang.,Gong, Xiang.,Zhang, Wen.,Pu, Rong.,...&Li, Yaping.(2024).Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer.JOURNAL OF CONTROLLED RELEASE,376,138-148.
MLA Zheng, Chao,et al."Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer".JOURNAL OF CONTROLLED RELEASE 376(2024):138-148.

入库方式： OAI收割

来源：上海药物研究所

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