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Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles

文献类型：期刊论文

作者Zheng, Chao8,9,10,11; Zhang, Wen8,10,11; Gong, Xiang8,10,11; Xiong, Fengqin8,10,11; Jiang, Linyang10,11; Zhou, Lingli10,11; Zhang, Yuan7; Zhu, Helen He5,6; Wang, Hao8; Li, Yaping2,3,4,10,11
刊名SCIENCE ADVANCES
出版日期2024-06-05
卷号10期号:23页码:16
ISSN号2375-2548
DOI10.1126/sciadv.adk9996
通讯作者Wang, Hao(wanghao99@hotmail.com) ; Li, Yaping(ypli@simm.ac.cn) ; Zhang, Pengcheng(zhangpch1@shanghaitech.edu.cn)
英文摘要Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (D-E-sHDL) or chemically conjugated ((c) D-sHDL) DM1. We found that (c) D-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than D-E-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving (c) D-sHDL, leading to a better efficacy and immune memory of (c) D-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 ((c) D-Lipo) showed lower immunotoxicity than those with entrapped drug (D-E-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.
WOS关键词PROTEIN ; NEUTRALIZATION ; APOLIPOPROTEIN ; RECRUITMENT ; PACLITAXEL ; EFFICACY ; TUMORS ; CELLS ; FORM
资助项目National Key R&d Program of china[2022YFc3401404] ; 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[32130058] ; Shandong laboratory Program[SYS202205] ; Natural Science Foundation of Shandong[ZR2019Zd25]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001244530600022
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/311926]  
专题新药研究国家重点实验室
通讯作者Wang, Hao; Li, Yaping; Zhang, Pengcheng
作者单位1.ShanghaiTech Univ, Sch Biomed Engn, Shanghai 201210, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai 200127, Peoples R China
6.Shanghai Jiao Tong Univ, Ren Ji Hosp, Dept Urol, State Key Lab Oncogenes & Related Genes,Renji Med, Shanghai 200127, Peoples R China
7.Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Pulm & Crit Care Med, Shanghai 200433, Peoples R China
8.China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China
9.Fudan Univ, Sch Pharm, Dept Pharmaceut, Shanghai 201203, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Chao,Zhang, Wen,Gong, Xiang,et al. Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles[J]. SCIENCE ADVANCES,2024,10(23):16.
APA Zheng, Chao.,Zhang, Wen.,Gong, Xiang.,Xiong, Fengqin.,Jiang, Linyang.,...&Zhang, Pengcheng.(2024).Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.SCIENCE ADVANCES,10(23),16.
MLA Zheng, Chao,et al."Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles".SCIENCE ADVANCES 10.23(2024):16.

入库方式： OAI收割

来源：上海药物研究所

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