Targeting rectal cancer using fluorescent nanoparticles conjugated to a novel GRPR-Binding peptide for tumor imaging applications

Abstract

Surgical treatment of rectal cancer is difficult due to anatomical complexity. To improve tumor resection, fluorescence-guided surgery (FGS) has been developed using near-infrared fluorescence (NIRF, approximately 800 nm) and a dedicated camera system. Indocyanine green (ICG), an FDA-approved NIRF probe, enables optical imaging. The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor family, is widely expressed in rectal cancer cells. This abundant expression makes GRPR an ideal biomarker for molecular targeting and imaging of rectal cancer. In this study, the location and expression levels of GRPR were measured by immunofluorescence, immunohistochemistry and western blot. Our data confirmed significant overexpression of GRPR in rectal cancer cells and tissue samples, providing a significant indication for GRPR targeting evaluation. We designed the novel GRPR-targeting peptide, GRP-derived peptide (GRP-DP) derived from the natural GRPR-binding gastrin-releasing peptide (GRP). The newly developed GRP-DP demonstrated strong in vitro GRPR-targeting capabilities for rectal cancer imaging, potentially aiding surgeons in achieving complete tumor resection. Additionally, we investigated the use of ICG encapsulated within poly(lactic-co-glycolic acid)-polyethylene glycol (ICG/PLGA-PEG) nanoparticles (NPs) as a vehicle for fluorescent tumor imaging in rectal cancer. The ICG-NPs were functionalized with GRP-DP, exhibiting favorable physicochemical properties, including controlled ICG release kinetics and biocompatibility.