GCN5-targeted dual-modal probe across the blood-brain barrier for borders display in invasive glioblastoma

Haiyan Zheng, Lu Zhang, Xinning Bai, Jinchao Zhu, Shanshan Liu, Yao Ke, Qingyuan Lin, Yuan Yuan and Tianhai Ji ()
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Haiyan Zheng: Shanghai Jiao Tong University School of Medicine
Lu Zhang: Changhai Hospital affiliated to Naval Medical University
Xinning Bai: Shanghai Jiao Tong University School of Medicine
Jinchao Zhu: Shanghai Jiao Tong University School of Medicine
Shanshan Liu: Xiamen University
Yao Ke: Shanghai Jiao Tong University School of Medicine
Qingyuan Lin: Shanghai Jiao Tong University School of Medicine
Yuan Yuan: Shanghai Jiao Tong University School of Medicine
Tianhai Ji: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Glioblastoma (GBM) is a highly invasive malignancy with a poor prognosis, primarily attributable to its diffuse infiltration into adjacent brain tissue, thereby complicating effective surgical resection. Current imaging modalities often struggle to accurately identify tumor boundaries. Here, we identify general control non-repressed protein 5 (GCN5) as a promising molecular target for GBM imaging, as it is expressed in GBM lesions within brain tissue, and its expression levels are significantly correlated with GBM grading. We develop a dual-modal probe with a particle size of 20 nm, capable of efficiently traversing the blood-brain barrier (BBB) to target GCN5 through adsorptive-mediated transcytosis (AMT). The probe employs dendrimers (Den) as carriers, which are loaded with a small molecule inhibitor specifically designed to target GCN5. This probe enhances the preoperative delineation of GBM boundaries using magnetic resonance imaging (MRI) and facilitates intraoperative fluorescence image-guided surgical procedures. Our work introduces a promising tool for boundary delineation, offering new opportunities for the precise resection of GBM.

Date: 2025
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DOI: 10.1038/s41467-025-57598-9

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