Dendron-Grafted Polylysine-Based Dual-Modal Nanoprobe for Ultra-Early Diagnosis of Pancreatic Precancerosis via Targeting a Urokinase-Type Plasminogen Activator Receptor.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer death. Early detection of precancerous pancreatic intraepithelial neoplasia (PanIN) tissues is an urgent challenge to improve the PDAC prognosis. Here, a urokinase-type plasminogen activator receptor (uPAR)-targeted magnetic resonance (MR)/near-infrared fluorescence (NIRF) dual-modal nanoprobe dendron-grafted polylysine (DGL)-U11 for ultra-early detection of pancreatic precancerosis is reported. Because of its good biocompatibility and biodegradability, globular architecture, and well-defined reactive groups, the DGL is chosen as the platform to load with a pancreatic tumor-targeting peptide U11, a magnetic resonance contrast agent Gd3+ -diethylene triamine pentaacetic acid, and a near-infrared fluorescent cyanine dye Cy5.5. The nanoprobe DGL-U11 has several preferable characteristics, such as active peptide targeting to activator receptor, good biocompatibility, dual-modal imaging diagnosis, and well controlled diameter in a range of 15-25 nm. Upon incorporation of the active U11 peptide target to the overexpressed activator receptor uPAR, the targeted nanoprobe DGL-U11 can increase to the earlier PanIN-II stage through in vivo NIRF imaging. Labeled with both MR and NIRF bioimaging reporters, the uPAR-targeted dual-modal nanoprobe is very effective in the targeted imaging of precancerous PanINs and PDAC lesions with high sensitivity and spatial resolution, providing a promising platform to the ultra-early detection of PDAC.