title: Effect of integrin receptor-targeted liposomal paclitaxel for hepatocellular carcinoma targeting and therapy.
abstract: The major aim of the present study was to develop an integrin receptor-targeted liposomal paclitaxel (PTX) to enhance the targeting specificity and therapeutic effect of PTX on hepatocellular carcinoma (HCC) cells. The specific Arg-Gly-Asp (RGD) ligand was conjugated to 1,2-distearoylphosphatidylethanolamine-polyethylene glycol 2000 to prepare the RGD-modified liposomes (RGD-LP). Furthermore, physicochemical characteristics of RGD-LP, including particle size, ζ potential, encapsulation efficiency andin vitroPTX release, were evaluated. RGD-modified liposomes were selected as the carrier for the present study, as they exhibit good biocompatibility and are easy to modify using RGD. The cellular uptake efficacy of RGD-LP by HepG2 cells was 3.3-fold higher than that of liposomes without RGD, indicating that RGD-LP may specifically target HepG2 cells by overexpressing integrin αvβ3 receptors. The RGD modification appeared to enhance the anti-proliferative activity of LP-PTX against HepG2 cells, with the extent of anti-proliferative activity dependent on the concentration of PTX and the incubation time. Additionally, evaluation of the homing specificity and anticancer efficacy of RGD-LP on the tumor spheroids indicated that solid tumor penetration was enhanced by the modification of RGD. In agreement with thesein vitrofindings,in vivoinvestigations demonstrated that RGD-LP-PTX exhibited a greater inhibitory effect on tumor growth in HepG2-bearing mice than LP-PTX or free PTX. Thus, RGD-LPs may represent an efficient targeted PTX delivery system for the treatment of patients with HCC.
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Liyu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Weiya
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
keywords: integrin receptor; liposome; paclitaxel; tumor targeting