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

[Display omitted] 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 6w/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.