Magnetic resonance/fluorescence dual-modality contrast agents targeting αvβ6-overexpressing tumors based on A20FMDV2 peptide as a ligand

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a malignant digestive system tumor with a poor late-stage prognosis. This study aimed to identify new methods for the early detection of PDAC. The nanoprobe A20FMDV2-Gd-5-FAM was developed using A20FMDV2 (N1AVPNLRGDLQVLAQKVART20-NH2, A20FMDV2) as the ligand and characterized using dynamic light scattering, transmission electron microscopy, Fourier transform infrared analysis, and UV absorption spectroscopy. The binding of pancreatic cancer cells AsPC-1, MIA PaCa-2, and normal human pancreatic H6C7 cells (HPDE6-C7) to the probe was verified using laser confocal microscopy, and the biocompatibility of the probe was evaluated in vivo. In vivo magnetic resonance and fluorescence imaging were also performed on nude mice with subcutaneous pancreatic tumor xenografts to verify the bimodal imaging performance of the probe. The probe exhibited good stability and biocompatibility and an enhanced relaxation rate (25.46 ± 1.32 mM−1 s−1) than Gd-DTPA. Confocal laser scanning microscopy results revealed that the A20FMDV2-Gd-5-FAM probe could be successfully ingested and internalized, and infrared analysis results demonstrated that the probe was linked successfully. Finally, magnetic resonance T1WI imaging and intravital fluorescence imaging demonstrated the specific signal enhancement of the probe at the tumor site. In conclusion, the bimodal molecular probe A20FMDV2-Gd-5-FAM showed a stable magnetic resonance and fluorescence bimodal imaging performance and is a promising new approach for diagnosing early-stage cancers with a high integrin αvβ6 expression.