A TAT-conjugated peptide inhibitor of polo-like kinase 1 for in vivo tumor imaging

Abstract

Abstract Early detection and accurate diagnosis are essential for the effective prevention and treatment of tumors. Optical imaging methods can provide real-time and high-resolution in vivo images for tumor diagnostic applications. Pro-Leu-His-Ser-Thr(PO3H2) (PLHSpT) is an inhibitor of polo-like kinase 1, which is overexpressed in various tumors, and the transactivator of transcription (TAT) is a peptide known to penetrate tumor cells. In this study, we used a fragment of the TAT sequence, YARVRRRGPRR, to produce a YARVRRRGPRR-conjugated PLHSpT peptide using solid-phase peptide synthesis. Subsequently, the cyanine 5 NHS ester (Cy5) fluorescent dye was attached to YARVRRRGPRRPLHSpT (1) to obtain the Cy5-YARVRRRGPRRPLHSpT peptide (2), which was used to identify tumor targets through optical imaging. 2 was injected into HeLa xenograft tumor-bearing mice. After in vivo imaging at 3 h, 6 h, and 24 h post-injection, mice were sacrificed for ex vivo fluorescence intensity assessment. Optical imaging scans of 2 revealed significantly high uptake by tumor cells at all in vivo scan times. The highest fluorescence intensity difference between tumor and muscles was observed at 6 h. Ex vivo results also showed a high variation in the tumor-to-muscle uptake ratios at 6 h. In conclusion, we synthesized and evaluated 2 for cancer diagnosis in mice. Our optical imaging results demonstrated that 2 has remarkable cancer-detection ability in vivo, establishing this peptide as a potential imaging probe for tumor diagnosis.

Keywords

• Peptide inhibitor
• Tumor diagnosis
• Optical imaging
• Polo-like kinase 1
• Transactivator of transcription
• YARVRRRGPRR-conjugated PLHSpT peptide