Modification of the C16Y peptide on nanoparticles is an effective approach to target endothelial and cancer cells via the integrin receptor

Abstract

Liposomes have been explored as potential drug and gene-delivery particles. In recent years, tumor-targeted liposomes have been developed to improve the efficacy of antitumor treatment. The C16Y peptide is a modified C16 peptide, which is derived from the laminin γ1 chain, and binds to integrins αvβ3 and α5β1 on endothelial cells. In this study, we prepared integrin-targeted C16Y peptide-modified liposomes (C16Y-L) to enhance the intracellular uptake of drugs and genes specifically into tumor tissues. The selectivity of C16Y-L for endothelial cells and cancer cells, which strongly express integrins αvβ3 and α5β1, was assessed by flow cytometry and confocal microscopy. The cellular uptake of C16Y-L by both cell types was higher than uptake of the un-labeled and scramble peptide-modified liposomes. Next, to ascertain the involvement of receptor-mediated endocytosis in the process, these cells were treated with C16Y-L for 1h at 37°C or at 4°C. We found that uptake was also dependent on the temperature. Moreover, to evaluate whether the uptake depended on an integrin–ligand interaction, we examined the inhibition of C16Y-L uptake using recombinant integrin αVβ3 and found that the cellular uptake of C16Y-L treated with αVβ3 integrin decreased. This result suggests that C16Y-L can selectively target cells that highly express integrin αVβ3. Thus, the modification of the C16Y peptide on a Drug Delivery System (DDS) carrier may be a feasible approach for drug or gene delivery into tumors.