title: RGD-modified lipid disks as drug carriers for tumor targeted drug delivery.
abstract: Melittin, the major component of the European bee venom, is a potential anticancer candidate due to its lytic properties. However, in vivo applications of melittin are limited due to its main side effect, hemolysis, especially when applied through intravenous administration. The polyethylene glycol-stabilized lipid disk is a novel type of nanocarrier, and the rim of lipid disks has a high affinity to amphiphilic peptides. In our study, a c(RGDyK) modified lipid disk was developed as a tumor targeted drug delivery system for melittin. Cryo-TEM was used to confirm the shape and size of lipid disks with or without c(RGDyK) modification. In vitro and in vivo hemolysis analyses revealed that the hemolysis effect significantly decreased after melittin associated with lipid disks. Importantly, the results of our in vivo biodistribution and tumor growth inhibitory experiments showed that c(RGDyK) modification increased the distribution of lipid disks in the tumor and the anticancer efficacy of melittin loaded lipid disks. Thus, we successfully achieved a targeted drug delivery system for melittin and other amphiphilic peptides with a good therapeutic effect and low side effects.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai, 201203, P. R. China. wylu@shmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Mingfei
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Yan
authors.forename: Yachao
authors.initials: Y
authors.lastname: Ren
authors.forename: Man
authors.initials: M
authors.lastname: Ying
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008555:Melitten / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D009842:Oligopeptides; D008555:Melitten; C047981:arginyl-glycyl-aspartic acid