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

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 IFNα 2 b, 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 IFNα 2 b.

Combination of gemcitabine-containing magnetoliposome and oxaliplatin-containing magnetoliposome in breast cancer treatment: A possible mechanism with potential for clinical application

“…GML and OML can weaken the effect of the sudden release of drug and remarkably increase the releasing time of the drug (Supplementary Figure S1). This finding may be ascribed to the strength of the drug-liposomal lipid interaction, fluidity of the bilayer, and half-life of the liposomal outer shell [41, 42]. …”

“…Moreover, animal studies indicated that CGOML under the guidance of an external magnetic field markedly reduced the tumor size of nude mice bearing human breast cancer (MCF-7) (Figures 5 and 6). Several drugs used for curing malignancies were reported to trigger apoptotic pathways [41]. Bax, a member of the Bcl-2 family, is an apoptosis promoter.…”

“…GML was prepared by a combined method of reverse-phase evaporation and water bath ultrasonication, as described by Ye [41] but with slight modifications. In this study, the dry lipid film was hydrated using a solution of gemcitabine dissolved in PBS and 10 nm Fe 3 O 4 .…”

“…In addition, the morphology, mean size, and size distribution of GML or OML were determined as described by Ye [41]. …”

“…The effects of GML and OML on platelets and leukocytes were examined using the method as described by Ye [41]. …”