Cyclic Arg-Gly-Asp Peptide-Labeled Liposomes for Targeting Drug Therapy of Hepatic Fibrosis in Rats

Abstract

Targeting hepatic stellate cells (HSCs) has been challenging due to the lack of specific receptors or motifs on the cells. The aim of the present study was to develop a HSC-specific system for improving drug delivery to HSCs. The affinity of a cyclic peptide containing Arg-Gly-Asp (cRGD) to collagen type VI receptor on HSCs was examined in both in vitro and in vivo experiments. Sterically stable liposomes (SSLs) were modified with this peptide to yield a new carrier, cRGD-SSL. The targeting efficiency of this carrier in delivering interferon (IFN)-␣1b was investigated in a rat model of liver fibrosis induced by bile duct ligation (BDL). When incubating HSCs or hepatocytes with cyclic RGD peptide, the peptide was bound preferentially to activated HSCs. Biodistribution study showed that the accumulation of cRGD peptide-labeled liposomes in HSCs isolated from BDL rats was 10-fold more than unlabeled SSLs. BDL rats receiving injections of IFN-␣1b entrapped in cRGD-SSL exhibited significantly reduced extent of liver fibrosis compared with BDL control rats or BDL rats treated with IFN-␣1b entrapped in SSLs. Thus, cRGD-SSL is an efficient drug carrier, which selectively targets activated HSCs and improves drug therapy for liver fibrosis to a significant extent. This liposomal formulation represents a new means of targeting drug carrier for the treatment of liver fibrosis, and it may have potential clinical applications.

Influence of PEGylation and RGD loading on the targeting properties of radiolabeled liposomal nanoparticles

“…This is in agreement with the results of Du et al who found an RGD dose-dependent uptake in hepatic stellate cells and an increased inhibition of hepatic stellate cell proliferation with cyclic RGD sterically stabilized liposomes. 42 The specific uptake in hepatic stellate cells increased with higher RGD loading of the sterically stabilized liposomes, which could be beneficial in treating liver fibrosis. These findings are in accordance with Shokeen et al who used multivalent, functional polymer nanoparticles (CNP) derivatized with varying amounts of a linear RGD peptide (5%, 10%, 20%, 50% RGD loading).…”

Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery

“…It has been reported that the RGD motif peptide, either in linear or cyclic form, recognizes Integrin αvβ3 and that it can be attached to the PEG-LPs or polyplex micelles for the successful delivery of drugs to target sites [35][36][37][38]. In this study, we attached the RGD motif peptide (cRGDfK) to the terminal ends of PEG molecules of PEG-LP as a single ligand system (RGD-PEG-LP) and STR-R8 was then attached to the surface of the lipid membrane of RGD-PEG-LP to prepare a dual-liagnd system (R8/RGD-PEG-LP), as shown in Fig.7.…”

RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy

“…The synthesis of FITC-labeled nanoparticles was based on the reaction between the isothiocyanate group of FITC and the primary amino group of nanoparticles. 28,29 Briefly, FITC was mixed with BSANPs in sodium bicarbonate buffer, pH 9.5, followed by incubation for 20-24 h in darkness at room temperature while stirring. It was then dialyzed against distilled water using a cellulose membrane (molecular weight cutoff 8,000-12,000) for 2 d and lyophilized.…”