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Comparative Study on Covalent and Noncovalent Endogenous Albumin-Binding β-Glucuronidase-Activated SN38 Prodrugs for Antitumor Efficacy

文献类型：期刊论文

作者Lu, Yingxin2; Jiang, Xing2; Yang, Biyu3; Ding, Mengyuan2,3; Shen, Yanyan3; Jin, Jiyu2; Yu, Jiahui2; Lu, Wei2; Chen, Yi1,3; Zhu, Shulei4,5
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2025-04-07
卷号68期号:8页码:8361-8376
ISSN号0022-2623
DOI10.1021/acs.jmedchem.4c03096
通讯作者Lu, Wei(wlu@chem.ecnu.edu.cn) ; Chen, Yi(ychen@simm.ac.cn) ; Zhu, Shulei(slzhu@chem.ecnu.edu.cn)
英文摘要Albumin-binding prodrugs have been explored to overcome the limitations of small-molecule anticancer chemotherapy agents, such as inadequate physiological and pharmaceutical compatibility, as well as rapid renal clearance. Herein, we investigated two endogenous albumin-binding prodrugs, M-g-SN38 and S-g-SN38, forming macromolecular conjugates. Both prodrugs exhibited robust stability in murine and human plasma, crucial for their therapeutic potential. Selective activation by beta-glucuronidase ensures minimal toxicity in their inactive state. Notably, M-g-SN38 exhibited higher cellular uptake, a longer circulation half-life, and enhanced tumor accumulation compared to S-g-SN38, suggesting its greater potential for improved antitumor efficacy. In vivo, M-g-SN38 exhibited significant antitumor activity, leading to profound tumor reduction and, in many cases, marked depletion and complete eradication in all treated mice in the HCT116 xenograft model. Furthermore, M-g-SN38 also demonstrated pronounced antitumor efficacy in the BxPC-3 xenograft model. Together, these findings provide new insights for the development of albumin-binding prodrugs.
WOS关键词RESPONSIVE DRUG-DELIVERY ; TUMOR MICROENVIRONMENT ; SERUM-ALBUMIN ; CAMPTOTHECIN ; DOXORUBICIN ; STRATEGIES ; CARRIER ; LINKER
资助项目National Natural Science Foundation of China[82104000] ; National Natural Science Foundation of China[22077034] ; National Natural Science Foundation of China[24QB2700300] ; Shanghai Rising-Star Program
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001460982500001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/316941]  
专题中国科学院上海药物研究所
通讯作者Lu, Wei; Chen, Yi; Zhu, Shulei
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China
2.East China Normal Univ, Sch Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Shanghai 200062, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
4.East China Normal Univ, Innovat Ctr AI & Drug Discovery, Shanghai 200062, Peoples R China
5.ATLATL Innovat Ctr, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Yingxin,Jiang, Xing,Yang, Biyu,et al. Comparative Study on Covalent and Noncovalent Endogenous Albumin-Binding β-Glucuronidase-Activated SN38 Prodrugs for Antitumor Efficacy[J]. JOURNAL OF MEDICINAL CHEMISTRY,2025,68(8):8361-8376.
APA Lu, Yingxin.,Jiang, Xing.,Yang, Biyu.,Ding, Mengyuan.,Shen, Yanyan.,...&Zhu, Shulei.(2025).Comparative Study on Covalent and Noncovalent Endogenous Albumin-Binding β-Glucuronidase-Activated SN38 Prodrugs for Antitumor Efficacy.JOURNAL OF MEDICINAL CHEMISTRY,68(8),8361-8376.
MLA Lu, Yingxin,et al."Comparative Study on Covalent and Noncovalent Endogenous Albumin-Binding β-Glucuronidase-Activated SN38 Prodrugs for Antitumor Efficacy".JOURNAL OF MEDICINAL CHEMISTRY 68.8(2025):8361-8376.

入库方式： OAI收割

来源：上海药物研究所

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