Optimization of cRGDfK ligand concentration on polymeric nanoparticles to maximize cancer targeting

Optimization of ligand density on polymeric nanoparticles (PNPs) is critical for targeting solid tumors. Here, we prepared fluorescent cyanine 5.5 dye and cyclo(arginine–glycine–aspartic acid–phenylalanine–lysine) ligand-modified polyethylene glycol-poly(lactic-co-glycolic acid) (Cy 5.5-cRGDfK-PEG-PLGA) NPs with different ligand concentrations and investigated their cancer-targeting abilities in vitro and in vivo. The PNPs self-assembled in an aqueous solution as round particles and showed an increase in their average size as a function of cRGDfK concentration. In vitro results revealed a gradual increase in the uptake of NPs in MDA-MB-435 breast cancer cells in a time- and ligand concentration-dependent manner. In vivo, NPs with 6 w/w% cRGDfK concentration showed prolonged uptake by the cancer tissue during the 7-day test period. These results suggest that Cy 5.5-cRGDfK₆-PEG-PLGA NPs could serve as valuable drug carriers and diagnostic agents for the clinical treatment and targeting of solid cancers.