Programmable Repurposing of Existing Drugs as Pharmaceutical Elements for the Construction of Aptamer-Drug Conjugates

doi:10.1021/acsami.0c18846

HFCAS OpenIR

	Programmable Repurposing of Existing Drugs as Pharmaceutical Elements for the Construction of Aptamer-Drug Conjugates
	Gao, Fei 1,2,3; Zhou, Jinming 4; Sun, Yang 1,2; Yang, Cai 1,2; Zhang, Shiyan 1,2; Wang, Ruowen 1,2; Tan, Weihong 1,2,5
	2021-03-03
发表期刊	ACS APPLIED MATERIALS & INTERFACES
ISSN	1944-8244
通讯作者	Wang, Ruowen(wangwrw@sjtu.edu.cn) ; Tan, Weihong(tan@hnu.edu.cn)
摘要	Converting marketed drug molecules into phos-phoramidites may present a potential strategy to facilitate the development of aptamer-drug conjugates (ApDCs) by a DNA synthesizer in a programmable way; however, quite limited methods were reported. Herein, we demonstrated a general approach by repurposing camptothecin (CPT) species. Commonly used inactive ingredients in pharmaceuticals are investigated and selected as a bonding moiety, from which 2-mercaptoethoxy ethanol and thioglycerol were efficiently incorporated with CPT to give the precursors. Cell viability and molecular docking results of the precursors supported that incorporation of the bonding moiety would not interrupt the inhibitory activity. Therefore, corresponding phosphoramidites were prepared as pharmaceutical elements, and a series of ApDCs were constructed automatically by solid-phase synthesis. Biological studies revealed that CPT elements could be specifically delivered to HCT116 cells by an aptamer and released inside cells. This kind of programmable repurposing may take advantage of established safety data and efficacy of existing drugs resulting in a faster development of ApDCs.
关键词	aptamer pharmaceutical elements solid-phase synthesis targeted therapy drug delivery
DOI	10.1021/acsami.0c18846
收录类别	SCI
语种	英语
资助项目	National Science Foundation of China[21877079] ; National Science Foundation of China[81803068]
项目资助者	National Science Foundation of China
WOS研究方向	Science & Technology - Other Topics ; Materials Science
WOS类目	Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS记录号	WOS:000626502700022
出版者	AMER CHEMICAL SOC
引用统计	被引频次：9[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.hfcas.ac.cn:8080/handle/334002/121087
专题	中国科学院合肥物质科学研究院
通讯作者	Wang, Ruowen; Tan, Weihong
作者单位	1.Shanghai Jiao Tong Univ, Inst Mol Med IMM, State Key Lab Oncogenes & Related Genes, Renji Hosp,Sch Med, Shanghai 200240, Peoples R China 2.Shanghai Jiao Tong Univ, Coll Chem & Chem Engn, Shanghai 200240, Peoples R China 3.Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China 4.Zhejiang Normal Univ, Dept Chem, Key Lab, Minist Educ Adv Catalysis Mat, 688 Yingbin Rd, Jinhua 321004, Zhejiang, Peoples R China 5.Univ Chinese Acad Sci, Chinese Acad Sci, Inst Basic Med & Canc IBMC, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Gao, Fei,Zhou, Jinming,Sun, Yang,et al. Programmable Repurposing of Existing Drugs as Pharmaceutical Elements for the Construction of Aptamer-Drug Conjugates[J]. ACS APPLIED MATERIALS & INTERFACES,2021,13.
APA	Gao, Fei.,Zhou, Jinming.,Sun, Yang.,Yang, Cai.,Zhang, Shiyan.,...&Tan, Weihong.(2021).Programmable Repurposing of Existing Drugs as Pharmaceutical Elements for the Construction of Aptamer-Drug Conjugates.ACS APPLIED MATERIALS & INTERFACES,13.
MLA	Gao, Fei,et al."Programmable Repurposing of Existing Drugs as Pharmaceutical Elements for the Construction of Aptamer-Drug Conjugates".ACS APPLIED MATERIALS & INTERFACES 13(2021).