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

文献类型：期刊论文

作者Yan, Feng2; Zhuang, Jianfeng2; Yu, Qian2; Dou, Zhangqi2; Jiang, Xuefeng2; Tan, Shuyu2; Han, Yifeng1; Wu, Xinyan2; Zang, Yi3; Li, Cong3
刊名ACS SENSORS
出版日期2021-09-24
卷号6期号:9页码:3330-3339
ISSN号2379-3694
关键词fluorescent probe bioinformatics analysis PDGFR beta glioma imaging glioma grading
DOI10.1021/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.
WOS关键词NERVOUS-SYSTEM ; DIAGNOSIS ; GROWTH ; TUMORS ; STATE
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
源URL[http://119.78.100.183/handle/2S10ELR8/297555]  
专题新药研究国家重点实验室
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.

入库方式： OAI收割

来源：上海药物研究所

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