Journal
ACS SENSORS
Volume 6, Issue 9, Pages 3330-3339Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssensors.1c01168
Keywords
fluorescent probe; bioinformatics analysis; PDGFR beta; glioma imaging; glioma grading
Funding
- National Key R&D Program of China [2018YFC1312600, 2018YFC1312603]
- National Natural Science Foundation of China [81971099, 81870908, 81801144, 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]
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Novel fluorescent probe design strategy targeting PDGFR beta successfully developed PDGFP 1 probe for accurate glioma imaging and grading. Experimental results demonstrated high selectivity and positive correlation with tumor grades in mouse models and patient samples, showing potential for clinical translation.
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.
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