Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma

Hui Ye,1,2 Jiansong Tong,2 Jianzhang Wu,3 Xia Xu,4 Shenjie Wu,5 Botao Tan,6 Mengjing Shi,5 Jianguang Wang,1 Weibo Zhao,5 Heng Jiang,5 Sha Jin5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cellular and Molecular Biology...

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Autores principales: Ye H, Tong JS, Wu JZ, Xu X, Wu SJ, Tan BT, Shi MJ, Wang JG, Zhao WB, Jiang H, Jin S
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:d8010bf037184188a1483eb2a4c977742021-12-02T02:42:29ZPreclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma1178-2013https://doaj.org/article/d8010bf037184188a1483eb2a4c977742014-09-01T00:00:00Zhttp://www.dovepress.com/preclinical-evaluation-of-recombinant-human-ifnalpha2b-containing-magn-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Hui Ye,1,2 Jiansong Tong,2 Jianzhang Wu,3 Xia Xu,4 Shenjie Wu,5 Botao Tan,6 Mengjing Shi,5 Jianguang Wang,1 Weibo Zhao,5 Heng Jiang,5 Sha Jin5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cellular and Molecular Biology, Scripps Research Institute, La Jolla, CA, USA; 3Pharmaceutical College, Wenzhou Medical University, Wenzhou, 4School of Medicine, Zhejiang University, Hangzhou, 5School of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, 6School of Medicine, Lishui University, Lishui, People’s Republic of China Abstract: Magnetoliposomes are phospholipid vesicles encapsulating magnetic nanoparticles that can be used to encapsulate therapeutic drugs for delivery into specific organs. Herein, we developed magnetoliposomes containing recombinant human IFNα2b, designated as MIL, and evaluated this combination’s biological safety and therapeutic effect on both cellular and animal hepatocellular carcinoma models. Our data showed that MIL neither hemolyzed erythrocytes nor affected platelet-aggregation rates in blood. Nitroblue tetrazolium-reducing testing showed that MIL did not change the absolute numbers or phagocytic activities of leukocytes. Acute-toxicity testing also showed that MIL had no devastating effect on mice behaviors. All the results indicated that the nanoparticles could be a safe biomaterial. Pharmacokinetic analysis and tissue-distribution studies showed that MIL maintained stable and sustained drug concentrations in target organs under a magnetic field, helped to increase bioavailability, and reduced administration time. MIL also dramatically inhibited the growth of hepatoma cells. Targeting of MIL in the livers of nude mice bearing human hepatocellular carcinoma showed that MIL significantly reduced the tumor size to 38% of that of the control group. Further studies proved that growth inhibition of cells or tumors was due to apoptosis-signaling pathway activation by human IFNα2b. Keywords: recombinant human interferon-α2b, magnetoliposome, hepatocellular carcinomaYe HTong JSWu JZXu XWu SJTan BTShi MJWang JGZhao WBJiang HJin SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4533-4550 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Ye H
Tong JS
Wu JZ
Xu X
Wu SJ
Tan BT
Shi MJ
Wang JG
Zhao WB
Jiang H
Jin S
Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
description Hui Ye,1,2 Jiansong Tong,2 Jianzhang Wu,3 Xia Xu,4 Shenjie Wu,5 Botao Tan,6 Mengjing Shi,5 Jianguang Wang,1 Weibo Zhao,5 Heng Jiang,5 Sha Jin5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cellular and Molecular Biology, Scripps Research Institute, La Jolla, CA, USA; 3Pharmaceutical College, Wenzhou Medical University, Wenzhou, 4School of Medicine, Zhejiang University, Hangzhou, 5School of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, 6School of Medicine, Lishui University, Lishui, People’s Republic of China Abstract: Magnetoliposomes are phospholipid vesicles encapsulating magnetic nanoparticles that can be used to encapsulate therapeutic drugs for delivery into specific organs. Herein, we developed magnetoliposomes containing recombinant human IFNα2b, designated as MIL, and evaluated this combination’s biological safety and therapeutic effect on both cellular and animal hepatocellular carcinoma models. Our data showed that MIL neither hemolyzed erythrocytes nor affected platelet-aggregation rates in blood. Nitroblue tetrazolium-reducing testing showed that MIL did not change the absolute numbers or phagocytic activities of leukocytes. Acute-toxicity testing also showed that MIL had no devastating effect on mice behaviors. All the results indicated that the nanoparticles could be a safe biomaterial. Pharmacokinetic analysis and tissue-distribution studies showed that MIL maintained stable and sustained drug concentrations in target organs under a magnetic field, helped to increase bioavailability, and reduced administration time. MIL also dramatically inhibited the growth of hepatoma cells. Targeting of MIL in the livers of nude mice bearing human hepatocellular carcinoma showed that MIL significantly reduced the tumor size to 38% of that of the control group. Further studies proved that growth inhibition of cells or tumors was due to apoptosis-signaling pathway activation by human IFNα2b. Keywords: recombinant human interferon-α2b, magnetoliposome, hepatocellular carcinoma
format article
author Ye H
Tong JS
Wu JZ
Xu X
Wu SJ
Tan BT
Shi MJ
Wang JG
Zhao WB
Jiang H
Jin S
author_facet Ye H
Tong JS
Wu JZ
Xu X
Wu SJ
Tan BT
Shi MJ
Wang JG
Zhao WB
Jiang H
Jin S
author_sort Ye H
title Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
title_short Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
title_full Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
title_fullStr Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
title_full_unstemmed Preclinical evaluation of recombinant human IFNα2b-containing magnetoliposomes for treating hepatocellular carcinoma
title_sort preclinical evaluation of recombinant human ifnα2b-containing magnetoliposomes for treating hepatocellular carcinoma
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/d8010bf037184188a1483eb2a4c97774
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