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 and in vitro PTX 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 these in vitro findings, in vivo investigations 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.