Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades

doi:10.1021/acssensors.1c01168

	Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades
	Yan, Feng 2; Zhuang, Jianfeng 2; Yu, Qian 2; Dou, Zhangqi 2; Jiang, Xuefeng 2; Tan, Shuyu 2; Han, Yifeng 1; Wu, Xinyan 2; Zang, Yi 3; Li, Cong 3
刊名	ACS SENSORS
	2021-09-24
卷号	6 期号:9 页码:3330-3339
关键词	fluorescent probe bioinformatics analysis PDGFR beta glioma imaging glioma grading
ISSN号	2379-3694
DOI	10.1021/acssensors.1c01168
通讯作者	Li, Xin(lixin81@zju.edu.cn) ; Chen, Gao(d-chengao@zju.edu.cn)
英文摘要	The extent of resection and tumor grade are two predominant prognostic factors for glioma. Fluorescent imaging is promising to facilitate accurate resection and simultaneous tumor grading. However, no probe fulfilling this task has been reported. Herein, we proposed a strategy of de novo design toward first-in-class fluorescent probes for simultaneously differentiating glioma boundary and grades. By bioinformatics analysis in combination with experimental validation, platelet-derived growth factor receptor beta (PDGFR beta) was revealed as a promising biomarker for glioma imaging and grading. Then, fluorogenic probe PDGFP 1 was designed, guided by the structure-activity relationship study. Finally, the probe was demonstrated to stain glioma cells and tissues in the mice orthotopic glioma model with high selectivity over normal brain cells or tissues. Meanwhile, ex vivo experiments using patient-derived samples indicated that the fluorescence was significantly positively correlated with the tumor grades. This result highlighted the feasibility of the three-step de novo probe design strategy and suggested PDGFP 1 as a promising probe for simultaneously differentiating glioma boundary and grades, showing prospects of clinical translation.
资助项目	National Key R&D Program of China[2018YFC1312600] ; National Key R&D Program of China[2018YFC1312603] ; National Natural Science Foundation of China[81971099] ; National Natural Science Foundation of China[81870908] ; National Natural Science Foundation of China[81801144] ; National Natural Science Foundation of China[81870910] ; Innovative Talents Plan of Zhejiang Province[2020380752] ; Scientific Research Fund of Zhejiang Provincial Education Department[Y201941838] ; Medical and Health Scientific Research Project of Zhejiang Province[2018KY408]
WOS关键词	NERVOUS-SYSTEM ; DIAGNOSIS ; GROWTH ; TUMORS ; STATE
WOS研究方向	Chemistry ; Science & Technology - Other Topics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000702090500021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297555]
专题	中国科学院上海药物研究所
通讯作者	Li, Xin; Chen, Gao
作者单位	1.Zhejiang Sci Tech Univ, Dept Chem, Hangzhou 310018, Peoples R China 2.Zhejiang Univ, Affiliated Hosp 2, Coll Pharmaceut Sci, Sch Med, Hangzhou 310058, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yan, Feng,Zhuang, Jianfeng,Yu, Qian,et al. Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades[J]. ACS SENSORS,2021,6(9):3330-3339.
APA	Yan, Feng.,Zhuang, Jianfeng.,Yu, Qian.,Dou, Zhangqi.,Jiang, Xuefeng.,...&Chen, Gao.(2021).Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades.ACS SENSORS,6(9),3330-3339.
MLA	Yan, Feng,et al."Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades".ACS SENSORS 6.9(2021):3330-3339.