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

Authors Wei MY, Guo XC, Tu LX, Zou Q, Li Q, Tang CY, Chen B, Xu YH, Wu CB

Received 20 April 2015

Accepted for publication 7 June 2015

Published 12 August 2015 Volume 2015:10(1) Pages 5123—5137

DOI https://doi.org/10.2147/IJN.S87011

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Lei Yang

Minyan Wei,1,2 Xiucai Guo,1,3 Liuxiao Tu,1 Qi Zou,1 Qi Li,1 Chenyi Tang,1 Bao Chen,1 Yuehong Xu,1 Chuanbin Wu1

1Department of Pharmaceutics, School of Pharmaceutical Sciences, Sun Yat-sen University, 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Guangzhou Medical University, 3Department of Pharmacy, 12th People’s Hospital of Guangzhou City, Guangzhou, People’s Republic of China

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.

Keywords: asialoglycoprotein receptor, immunoliposome, PEGylated modification, post-insertion, hepatic cancer, active targeting

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