title: [In vitro targeting effect of lactoferrin modified PEGylated liposomes for hepatoma cells].
abstract: A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.
authors.forename: Min-yan
authors.initials: MY
authors.lastname: Wei
authors.forename: Qi
authors.initials: Q
authors.lastname: Zou
authors.forename: Chuan-bin
authors.initials: CB
authors.lastname: Wu
authors.forename: Yue-hong
authors.initials: YH
authors.lastname: Xu
mesh_terms: D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D003374:Coumarins; D016503:Drug Delivery Systems; D004705:Endocytosis; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D008081:Liposomes; D008113:Liver Neoplasms / Q000473:pathology*; D010316:Particle Size; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D013844:Thiazoles
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D037263:Asialoglycoprotein Receptor; D003374:Coumarins; D008081:Liposomes; D010714:Phosphatidylethanolamines; D013844:Thiazoles; C517282:coumarin 6; D011092:Polyethylene Glycols; D007781:Lactoferrin