SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy

doi:10.1016/j.jconrel.2021.09.040

	SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy
	Huang, Ying 1; Wang, Lei 1; Cheng, Zhiyang 1; Yang, Biyu 2; Yu, Jiahui 1; Chen, Yi 2; Lu, Wei 1
刊名	JOURNAL OF CONTROLLED RELEASE
	2021-11-10
卷号	339 页码:297-306
关键词	Antitumour Chemotherapy SN38 Drug delivery systems Albumin
ISSN号	0168-3659
DOI	10.1016/j.jconrel.2021.09.040
通讯作者	Wang, Lei(lwang@chem.ecnu.edu.cn) ; Chen, Yi(ychen@simm.ac.cn) ; Lu, Wei(wlu@chem.ecnu.edu.cn)
英文摘要	Developing new therapeutic strategies that damage tumour cells without harming normal tissues is among the primary obstacles in chemotherapy. In this study, a novel 13-glucuronidase-sensitive albumin-binding prodrug was designed and synthesized to selectively deliver the drug SN38 to tumour sites and maximize its efficacy. After intravenous administration, the prodrug Mal-glu-SN38 covalently bound to plasma albumin through the Michael addition, enabling it to accumulate in the tumour and release SN38 when triggered by extracellular 13-glucuronidase. Compared to irinotecan, Mal-glu-SN38 displayed a slower plasma clearance and increased drug exposure over time. Moreover, Mal-glu-SN38 caused an increase in tumour-site accumulation of both the albumin-prodrug conjugate and free SN38 released from albumin conjugate when compared with irinotecan. After administration of multiple doses, Mal-glu-SN38 also significantly delayed the tumour growth, resulting in an impressive reduction or even disappearance of tumours (67% of mice cured) without causing any observable side effects.
资助项目	Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China[22077034]
WOS关键词	TOPOISOMERASE-I INHIBITORS ; DRUG-DELIVERY ; NANOPARTICLES ; DOXORUBICIN ; EFFICACY ; CONJUGATE ; THERAPY ; VIVO
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000707425500003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298433]
专题	中国科学院上海药物研究所
通讯作者	Wang, Lei; Chen, Yi; Lu, Wei
作者单位	1.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Sch Chem & Mol Engn, 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	Huang, Ying,Wang, Lei,Cheng, Zhiyang,et al. SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy[J]. JOURNAL OF CONTROLLED RELEASE,2021,339:297-306.
APA	Huang, Ying.,Wang, Lei.,Cheng, Zhiyang.,Yang, Biyu.,Yu, Jiahui.,...&Lu, Wei.(2021).SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy.JOURNAL OF CONTROLLED RELEASE,339,297-306.
MLA	Huang, Ying,et al."SN38-based albumin-binding prodrug for efficient targeted cancer chemotherapy".JOURNAL OF CONTROLLED RELEASE 339(2021):297-306.