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Strategy of De Novo Design toward First-In-Class Imaging Agents for Simultaneously Differentiating Glioma Boundary and Grades
ACS Sensors ( IF 8.2 ) Pub Date : 2021-08-27 , DOI: 10.1021/acssensors.1c01168 Feng Yan 1 , Jianfeng Zhuang 1 , Qian Yu 1 , Zhangqi Dou 1 , Xuefeng Jiang 1 , Shuyu Tan 1 , Yifeng Han 2 , Xinyan Wu 1 , Yi Zang 3 , Cong Li 3 , Jia Li 3 , Huaijun Chen 1 , Libin Hu 1 , Xin Li 1 , Gao Chen 1
ACS Sensors ( IF 8.2 ) Pub Date : 2021-08-27 , DOI: 10.1021/acssensors.1c01168 Feng Yan 1 , Jianfeng Zhuang 1 , Qian Yu 1 , Zhangqi Dou 1 , Xuefeng Jiang 1 , Shuyu Tan 1 , Yifeng Han 2 , Xinyan Wu 1 , Yi Zang 3 , Cong Li 3 , Jia Li 3 , Huaijun Chen 1 , Libin Hu 1 , Xin Li 1 , Gao Chen 1
Affiliation
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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 β (PDGFRβ) 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.
中文翻译：
用于同时区分胶质瘤边界和等级的一流成像代理的从头设计策略
切除范围和肿瘤分级是胶质瘤的两个主要预后因素。荧光成像有望促进准确切除和同步肿瘤分级。但是，尚未报告完成此任务的探针。在此，我们提出了一种从头设计的策略，用于同时区分胶质瘤边界和等级的一流荧光探针。通过生物信息学分析结合实验验证，血小板衍生生长因子受体β（PDGFRβ）被揭示为胶质瘤成像和分级的有希望的生物标志物。然后，荧光探针PDGFP 1是在构效关系研究的指导下设计的。最后，该探针被证明可以对小鼠原位神经胶质瘤模型中的神经胶质瘤细胞和组织进行染色，其选择性高于正常脑细胞或组织。同时，使用患者来源样本的离体实验表明，荧光与肿瘤分级显着正相关。该结果突出了三步从头探针设计策略的可行性，并建议PDGFP 1作为同时区分神经胶质瘤边界和等级的有前途的探针，显示出临床转化的前景。
更新日期：2021-09-24
中文翻译：
用于同时区分胶质瘤边界和等级的一流成像代理的从头设计策略
切除范围和肿瘤分级是胶质瘤的两个主要预后因素。荧光成像有望促进准确切除和同步肿瘤分级。但是，尚未报告完成此任务的探针。在此，我们提出了一种从头设计的策略，用于同时区分胶质瘤边界和等级的一流荧光探针。通过生物信息学分析结合实验验证，血小板衍生生长因子受体β（PDGFRβ）被揭示为胶质瘤成像和分级的有希望的生物标志物。然后，荧光探针PDGFP 1是在构效关系研究的指导下设计的。最后，该探针被证明可以对小鼠原位神经胶质瘤模型中的神经胶质瘤细胞和组织进行染色，其选择性高于正常脑细胞或组织。同时，使用患者来源样本的离体实验表明，荧光与肿瘤分级显着正相关。该结果突出了三步从头探针设计策略的可行性，并建议PDGFP 1作为同时区分神经胶质瘤边界和等级的有前途的探针，显示出临床转化的前景。
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