Human Glioblastoma Visualization: Triple Receptor-Targeting Fluorescent Complex of Dye, SIWV Tetra-Peptide, and Serum Albumin Protein

Abstract

Fluorescence guided surgery (FGS) has been highlighted in the clinical site for guiding surgical procedures and providing the surgeon with a real-time visualization of the operating field. FGS is a powerful technique for precise surgery, particularly tumor resection; however, clinically approved fluorescent dyes have often shown several limitations during FGS, such as non-tumor-targeting, low in vivo stability, insufficient emission intensity, and low blood-brain barrier penetration. In this study, we disclose a fluorescent dye complex, peptide, and protein for the targeted visualization of human glioblastoma (GBM) cells and tissues. Our noble triple receptor-targeting fluorescent complex (named <b>BSA-OXN-SIWV</b>) consists of (i) dipolar oxazepine dye (<b>OXN</b>), which has high stability, low cytotoxicity, bright fluorescence, and two-photon excitable, (ii) tetra-peptide (SIWV) for the targeting of the caveolin-1 receptor, and (iii) bovine serum-albumin (BSA) protein for the targeting of albondin (gp60) and secreted protein acidic and rich in cysteine receptor. The photophysical properties and binding mode of <b>BSA-OXN-SIWV</b> were analyzed, and the imaging of GBM cell lines and human clinical GBM tissues were successfully demonstrated in this study. Our findings hold great promise for the application of <b>BSA-OXN-SIWV</b> to GBM identification and the surgery at clinical sites, as a new FGS agent.