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

doi:10.1016/j.jconrel.2024.09.047

	Cabozantinib-encapsulated and maytansine-conjugated high-density lipoprotein for immunotherapy in colorectal cancer
	Zheng, Chao 1,2,3,4,5; Jiang, Linyang 3,4,6; Gong, Xiang 3,4,5; Zhang, Wen 3,4,5; Pu, Rong 3,4,7; Zhang, Yuan 8; Zhao, Mengmeng 8; Jiang, Chen 1,2; Wang, Hao 1,2,5; Zhang, Pengcheng9,10,11 ; Li, Yaping 3,4,6,7,12,13
	2024-12-01
发表期刊	JOURNAL OF CONTROLLED RELEASE (IF:10.5[JCR-2023],10.6[5-Year])
ISSN	0168-3659
EISSN	1873-4995
卷号	376 页码:138-148
发表状态	已发表
DOI	10.1016/j.jconrel.2024.09.047
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.
关键词	Synthetic high-density lipoprotein Cabozantinib Maytansine Myeloid-derived suppressor cell Immunosuppression Colorectal cancer
URL	查看原文
收录类别	EI ; SCI
语种	英语
资助项目	National Key Research and Development Program of China[2022YFC3401400] ; National Natural Science Foundation of China["32171374","32371457","82270064","82100073"] ; Shandong Provincial Natural Science Foundation[ZR2019ZD25] ; Shandong Laboratory Program[SYS202205]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号	WOS:001347568600001
出版者	ELSEVIER
EI入藏号	20244117177945
EI主题词	Cell death
EI分类号	103 ; 103.2
原始文献类型	Journal article (JA)
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/436538
专题	生物医学工程学院_PI研究组_张鹏程组
通讯作者	Jiang, Chen; Wang, Hao; Zhang, Pengcheng; Li, Yaping
作者单位	1.Fudan Univ, Sch Pharm, State Key Lab Med Neurobiol, Key Lab Smart Drug Delivery,Minist Educ,Dept Pharm, Shanghai 201203, Peoples R China 2.MOE Frontiers Ctr Brain Sci, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 5.China State Inst Pharmaceut Ind, Natl Adv Med Engn Res Ctr, Shanghai 201203, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China 8.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pulm & Crit Care Med, Shanghai 200433, Peoples R China 9.ShanghaiTech Univ, Sch Biomed Engn, State Key Lab Adv Med Mat & Devices, Shanghai 201210, Peoples R China 10.ShanghaiTech Univ, State Key Lab Adv Med Mat & Devices, Shanghai 201210, Peoples R China 11.Shanghai Clin Res & Trial Ctr, Shanghai 201203, Peoples R China 12.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China 13.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
通讯作者单位	生物医学工程学院; 上海科技大学
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.