Hepatocellular carcinoma targeting effect of PEGylated liposomes modified with lactoferrin

A hepatocellular carcinoma targeting lactoferrin (Lf) modified PEGylated liposome system was developed for improving drug efficacies to hepatic cancer cells. In this present work, PEGylated liposomes (PLS) were successfully prepared by the thin film hydration method combined with peglipid post insertion. Lf was covalently conjugated to the distal end of DSPE-PEG2000-COOH lipid by amide bound and loaded onto PEGylated liposomes surface as the targeting ligand. To confirm the targeting efficacies to hepatic cancer, coumarin-6 and DiR were encapsulated as fluorescent probes. The confocal microscopy and flow cytometry demonstrated that Lf conjugated PEGylated liposomes (Lf-PLS) were efficiently associated by HepG2 cells, while limited interaction was found for liposomes modified with a negative control protein. A similar pharmacokinetic behavior was observed in pharmacokinetics study of the liposomal formulations. Meanwhile, the in vivo imaging of liposomes in HepG2 tumor bearing mice indicated that Lf-PLS achieved more accumulation in tumor compared with PLS without Lf conjugated. The significant in vitro and in vivo results suggested that Lf-PLS might be a promising drug delivery system for hepatocellular carcinoma therapy with low toxicity.