Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo

Min-Chen Liu,1 Lin Liu,1 Xia-Rong Wang,1 Wu-Ping Shuai,2 Ying Hu,3 Min Han,1 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, People’s R...

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Autores principales:	Liu MC, Liu L, Wang XR, Shuai WP, Hu Y, Han M, Gao JQ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	active targeting PEGylated liposome diacid metabolite of norcantharidin hepatic cancer Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8e124a714a6d45f381ed654803a72651
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spelling	oai:doaj.org-article:8e124a714a6d45f381ed654803a726512021-12-02T07:13:42ZFolate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo1178-2013https://doaj.org/article/8e124a714a6d45f381ed654803a726512016-04-01T00:00:00Zhttps://www.dovepress.com/folate-receptor-targeted-liposomes-loaded-with-a-diacid-metabolite-of--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Min-Chen Liu,1 Lin Liu,1 Xia-Rong Wang,1 Wu-Ping Shuai,2 Ying Hu,3 Min Han,1 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, People’s Republic of China Abstract: The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (P<0.01). We used liquid chromatography–mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments (P<0.01). Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (P<0.01), and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues of model mice or the liver tissue of normal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy. Keywords: active targeting, PEGylated liposome, diacid metabolite of norcantharidin, hepatic cancerLiu MCLiu LWang XRShuai WPHu YHan MGao JQDove Medical Pressarticleactive targetingPEGylated liposomediacid metabolite of norcantharidinhepatic cancerMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1395-1412 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	active targeting PEGylated liposome diacid metabolite of norcantharidin hepatic cancer Medicine (General) R5-920
spellingShingle	active targeting PEGylated liposome diacid metabolite of norcantharidin hepatic cancer Medicine (General) R5-920 Liu MC Liu L Wang XR Shuai WP Hu Y Han M Gao JQ Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
description	Min-Chen Liu,1 Lin Liu,1 Xia-Rong Wang,1 Wu-Ping Shuai,2 Ying Hu,3 Min Han,1 Jian-Qing Gao1 1Institute of Pharmaceutics, College of Pharmaceutical Sciences, 2First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 3Zhejiang Pharmaceutical College, Ningbo, People’s Republic of China Abstract: The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (P<0.01). We used liquid chromatography–mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments (P<0.01). Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (P<0.01), and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues of model mice or the liver tissue of normal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy. Keywords: active targeting, PEGylated liposome, diacid metabolite of norcantharidin, hepatic cancer
format	article
author	Liu MC Liu L Wang XR Shuai WP Hu Y Han M Gao JQ
author_facet	Liu MC Liu L Wang XR Shuai WP Hu Y Han M Gao JQ
author_sort	Liu MC
title	Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
title_short	Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
title_full	Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
title_fullStr	Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
title_full_unstemmed	Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo
title_sort	folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for h22 hepatocellular carcinoma both in vitro and in vivo
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/8e124a714a6d45f381ed654803a72651
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Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo

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