366. Development of Engineered Magnetic Nanoparticles Coupled With Lentiviral Vectors for Targeted Cancer Therapy and Hyperthermia

Abstract

BackgroundIn recent years, considerable efforts have been spent to develop magnetic nanoparticles (MNPs) and to improve their applicability in several areas including hyperthermia and target cancer gene therapies.The aim of the present study was to synthesize and characterize Fe3O4, magnetite core-silica shell and magnetite core-silica shell doped with calcium ions nanoparticles (NPs) in combination with lentiviral vectors to deliver therapeutic genes in vivo.Materials and MethodsMagnetite NPs were prepared by co-precipitation method, the silica shell was obtained by wet chemistry on the magnetic core stabilized with citric acid. Calcium ions were added to the silica shell modulating the NPs surface reactivity.The NPs were characterized with X-Ray diffraction, transmission electron microscopy, Vibrating Sample Magnetometer and zeta potential.Cytocompatibility tests were performed using both direct and not-direct contact models with murine endothelial cells (MS1) both in static and dynamic conditions using MNP coupled with/out LV.MNP and MNP-LV were tail vein injected intravenously in C57/Bl6 mice, biodistribution and expression studies were performed by histology and immunofluorescence using GFP as a marker gene.ResultsSpherical magnetite nanoparticles of about 15 nm in diameter were obtained with good dispersion in water. Addition of silica and calcium allowed obtaining a thin and amorphous silica or Ca-enriched silica shell, maintaining good dispersion in water. All the MNPs displayed a superparamagnetic behaviour.The MNP+/-LV used demonstrated to be cytocompatible in both static traditional and dynamic cytocompatibility models. Moreover when MNP-LV injected in mice we detected GFP expression mainly in the liver and spleen with biodistribution differences based on the MNPs-LV combination used.ConclusionThese results suggest these NPs as promising for in vivo applications. Biodistribution studies in vivo of Fe3O4 NPs in mice models were performed and accumulation of NPs into vital organs was minimal with no toxicity in mice up to 1 month later and sustained GFP expression detected with no inflammatory responses. The present studies can significantly improve the cancer therapy effectiveness by means of a selective and localized delivery of transgenes together with the opportunity to conjugate hyperthermic and genetic approaches using therapeutic transgenes.