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

作者：Hamano Nobuhito; Negishi Yoichi^*; Fujisawa Azusa; Manandhar Maya; Sato Hinako; Katagiri Fumihiko; Nomizu Motoyoshi; Aramaki Yukihiko

来源：International Journal of Pharmaceutics, 2012, 428(1-2): 114-117.

DOI：10.1016/j.ijpharm.2012.02.006

• Liposomes
• Integrin
• Peptide
• Tumor targeting

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 gamma 1 chain, and binds to integrins alpha(v)beta 3 and alpha 5 beta 1 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 alpha(v)beta 3 and alpha 5 beta 1, 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 1 h at 37 degrees C or at 4 degrees 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 alpha V beta 3 and found that the cellular uptake of C16Y-L treated with alpha V beta 3 integrin decreased. This result suggests that C16Y-L can selectively target cells that highly express integrin alpha V beta 3. 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.

• 出版日期2012-5-30