Design and biological validation of magnetic NPs conjugated with chemotherapy drugs and viral vectors for anticancer therapy

Enrico CATALANO, Oslo University Hospital, Norway

During the last decade, significant scientific efforts have led to a significant growth in understanding of cancer at all biological levels providing great opportunities for  diagnosis and treatment of cancer diseases. The aim of the present study was to synthesize and characterize superparamagnetic iron oxide nanoparticles (SPIONs) in combination with drugs and viral vectors (VV) for their theranostics and hyperthermia treatment.

SPIONs were prepared by coprecipitation method, the silica shell was obtained by wet chemistry on the  magnetic core stabilized with citric acid. Magnetic nanoparticles were combined with chemotherapy drugs for liver cancer Nexavar and Sorafenib. The NPs were characterized from physicochemical point of view.

Cytocompatibility tests were performed with liver cancer cell line Hep G2. Biocompatibility and therapeutic efficacy of SPIONs, SPIONs/drugs and SPIONs-VV were evaluated by intravenously tail vein injection in mice, biodistribution and expression studies were performed by histology and immunofluorescence using Red Fluorescent Protein (RFP) as a marker gene.

Results.
Spherical magnetite nanoparticles of about 15 nm in diameter were obtained by the co-precipitation method. Stable suspensions in aqueous media were obtained by citric acid treatment All the NPs displayed a superparamagnetic behaviour. The NPs+/VV complexes used demonstrated to be cytocompatible in both static traditional and dynamic cytocompatibility models. Moreover when NPs-LV complexes injected in mice we detected RFP expression mainly in the liver and spleen with biodistribution differences based on the NPs-VV combination used. In vitro tests of MNPs/drugs for liver cancer demonstrated the dual effect of hyperthermia and targeted chemotherapy to be able in killing hepatic cancer cell lines. These results showed no inflammatory responses and no accumulation of NPs into vital organs. The present studies can improve device for theranostics and cancer therapy.

 
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