title: 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 α(v)β3 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 α(v)β3 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.
authors.affiliation: Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Negishi
authors.forename: Azusa
authors.initials: A
authors.lastname: Fujisawa
authors.forename: Maya
authors.initials: M
authors.lastname: Manandhar
authors.forename: Hinako
authors.initials: H
authors.lastname: Sato
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Aramaki
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000378:metabolism*; D018014:Gene Transfer Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D008081:Liposomes; D009842:Oligopeptides; C569383:aspartyl-phenylalanyl-lysyl-leucyl-phenylalanyl-alanyl-valyl-tyrosyl-isoleucyl-lysyl-tyrosyl-arginine; D011092:Polyethylene Glycols