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

Abstract

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