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

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, 3Dep...

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Autores principales: Wei MY, Guo XC, Tu LX, Zou Q, Li Q, Tang CY, Chen B, Xu YH, Wu CB
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:8905c217601542e4966e17366eb01a6d2021-12-02T01:49:55ZLactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma1178-2013https://doaj.org/article/8905c217601542e4966e17366eb01a6d2015-08-01T00:00:00Zhttp://www.dovepress.com/lactoferrin-modified-pegylated-liposomes-loaded-with-doxorubicin-for-t-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Minyan 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 targetingWei MYGuo XCTu LXZou QLi QTang CYChen BXu YHWu CBDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5123-5137 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wei MY
Guo XC
Tu LX
Zou Q
Li Q
Tang CY
Chen B
Xu YH
Wu CB
Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
description 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
format article
author Wei MY
Guo XC
Tu LX
Zou Q
Li Q
Tang CY
Chen B
Xu YH
Wu CB
author_facet Wei MY
Guo XC
Tu LX
Zou Q
Li Q
Tang CY
Chen B
Xu YH
Wu CB
author_sort Wei MY
title Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
title_short Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
title_full Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
title_fullStr Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
title_full_unstemmed Lactoferrin-modified PEGylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
title_sort lactoferrin-modified pegylated liposomes loaded with doxorubicin for targeting delivery to hepatocellular carcinoma
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/8905c217601542e4966e17366eb01a6d
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