Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma

• Published in: International journal of nanomedicine Vol. 10; pp. 5123 - 5137
• Main Authors: Wei, Minyan, Guo, Xiucai, Tu, Liuxiao, Zou, Qi, Li, Qi, Tang, Chenyi, Chen, Bao, Xu, Yuehong, Wu, Chuanbin
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2015; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: active targeting; Animals; Antineoplastic Agents - chemistry; Asialoglycoprotein Receptor; Biomedical materials; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Care and treatment; Cell Line; Cell Proliferation; Chromatography; Cytotoxicity; Dosage and administration; Doxorubicin; Doxorubicin - analogs & derivatives; Doxorubicin - chemistry; Drug delivery systems; Drugs; Flow Cytometry; Hep G2 Cells; hepatic cancer; Hepatoma; Humans; immunoliposome; Innovations; Laboratory animals; Lactoferrin - chemistry; Ligands; Lipids; Liposomes; Liposomes - chemistry; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Nanoparticles; NIH 3T3 Cells; Original Research; Particle Size; PEGylated modification; Pharmaceutical sciences; Polyethylene glycol; Polyethylene Glycols - chemistry; post-insertion; Thin films; Vehicles; Xenograft Model Antitumor Assays; Beijing China; United States > US; China; hepatic cancer; PEGylated modification; asialoglycoprotein receptor; active targeting; post-insertion; immunoliposome
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S87011

Lactoferrin (Lf) is a potential-targeting ligand for hepatocellular carcinoma (HCC) cells because of its specific binding with asialoglycoprotein receptor (ASGPR). In this present work, a doxorubicin (DOX)-loaded, Lf-modified, polyethylene glycol (PEG)ylated liposome (Lf-PLS) system was developed, and its targeting effect and antitumor efficacy to HCC was also explored. The DOX-loaded Lf-PLS system had spherical or oval vesicles, with mean particle size approximately 100 nm, and had an encapsulation efficiency of 97%. The confocal microscopy and flow cytometry indicated that the cellular uptake of Lf-PLS was significantly higher than that of PEGylated liposome (PLS) in ASGPR-positive cells (P<0.05) but not in ASGPR-negative cells (P>0.05). Cytotoxicity assay by MTT demonstrated that DOX-loaded Lf-PLS showed significantly stronger antiproliferative effects on ASGPR-positive HCC cells than did PLS without the Lf modification (P<0.05). The in vivo antitumor studies on male BALB/c nude mice bearing HepG2 xenografts demonstrated that DOX-loaded Lf-PLS had significantly stronger antitumor efficacy compared with PLS (P<0.05) and free DOX (P<0.05). All these results demonstrated that a DOX-loaded Lf-PLS might have great potential application for HCC-targeting therapy.