A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo

doi:10.1016/j.ejmech.2021.113851

	A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo
	Cheng, Zhiyang 1; Huang, Ying 1; Shen, Qianqian 2; Zhao, Yangrong 2; Wang, Lei 1; Yu, Jiahui 1; Lu, Wei 1
刊名	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
	2021-12-15
卷号	226 页码:11
关键词	Cancer beta-glucuronidase Bioconjugation Albumin Camptothecin
ISSN号	0223-5234
DOI	10.1016/j.ejmech.2021.113851
通讯作者	Wang, Lei(lwang@chem.ecnu.edu.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn)
英文摘要	The albumin-based drug delivery system is an effective drug delivery strategy for traditional chemotherapeutic drugs that can improve their antitumour efficacies and reduce systemic toxicities. The camptothecin derivative CPTS0001 has excellent antitumour activity in vitro, but it shows toxicity and side effects in vivo. In this study, we report the synthesis and biological evaluation of the beta-glucuronidase-reactive albumin-binding prodrug Mal-glu-CPTS0001 based on quaternary ammonium. After intravenous administration, the compound covalently binds to plasma albumin through Michael addition, enabling it to accumulate in tumours, where tumour-associated beta-glucuronidase triggers the selective release of CPTS0001. This prodrug significantly reduced the toxicity of the parent drug, and the maximum tolerated dose was increased by 2.5 times. At the same time, this prodrug enhanced the selectivity in vivo and improved the preferential accumulation of prodrug in tumours. Notably, this prodrug exhibited excellent in vivo antitumour effects in a murine breast cancer xenograft model without visible pathological toxicity. (C) 2021 Elsevier Masson SAS. All rights reserved.
资助项目	Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China[22077034]
WOS关键词	DRUG-DELIVERY ; BIOLOGICAL EVALUATION ; DERIVATIVES ; DOXORUBICIN ; NANOPARTICLES ; CONJUGATE ; RELEASE ; DESIGN ; VITRO
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000703119000033
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297452]
专题	中国科学院上海药物研究所
通讯作者	Wang, Lei; Lu, Wei
作者单位	1.East China Normal Univ, Sch Chem & Mol Engn, 3663 North Zhongshan Rd, Shanghai 200062, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Cheng, Zhiyang,Huang, Ying,Shen, Qianqian,et al. A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,226:11.
APA	Cheng, Zhiyang.,Huang, Ying.,Shen, Qianqian.,Zhao, Yangrong.,Wang, Lei.,...&Lu, Wei.(2021).A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,226,11.
MLA	Cheng, Zhiyang,et al."A camptothecin-based, albumin-binding prodrug enhances efficacy and safety in vivo".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 226(2021):11.