title: Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma.
abstract: 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.
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China ; Department of Pharmaceutics, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China.
authors: Minyan
authors: M
authors: Wei
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China ; Department of Pharmacy, 12th People's Hospital of Guangzhou City, Guangzhou, People's Republic of China.
authors: Xiucai
authors: X
authors: Guo
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Liuxiao
authors: L
authors: Tu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Qi
authors: Q
authors: Zou
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Qi
authors: Q
authors: Li
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Chenyi
authors: C
authors: Tang
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Bao
authors: B
authors: Chen
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Yuehong
authors: Y
authors: Xu
authors: Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors: Chuanbin
authors: C
authors: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D037263:Asialoglycoprotein Receptor; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D007781:Lactoferrin / Q000737:chemistry*; D008024:Ligands; D008081:Liposomes / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D037263:Asialoglycoprotein Receptor; C490098:LTF protein, human; D008024:Ligands; D008081:Liposomes; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D007781:Lactoferrin
keywords: PEGylated modification; active targeting; asialoglycoprotein receptor; hepatic cancer; immunoliposome; post-insertion