In Vitro Toxicology Assessment Of Dextran Magnetic Composite Nanoparticles As Targeting Drug Carrier

Magneticnanoparticles have attracted much attention because of its unique physical and chemical properties and widely potential application, such as clinical diagnostic, thermotherapy and targeted drug delivery. However, the toxicology assessment is still a challenge, which directly effects the application of magnetic nanoparticles in biomedical area. The dextran magnetic composite nanoparticles (DMNPs) have been approved by FDA to be used as a MRI contrast agent in clinical and are expected to be an ideal carrier for magnetic drug delivery. In this study, the cytotoxicity of the dextran magnetic particles and Doxrobincin (Dox)-loaded magnetic particles were evaluated in vitro with three different cell lines, including Human hepatocellular liver carcinoma cells HepG2, human normal liver cell LO2and endothelial cells EC. The interaction between dextran magneticcomposite nanoparticles (DMNPs) and cells were also discussed.1) The toxicity evaluation of DMNPs was investigated by examining the morphology, viability, mortality, membrane integrity, proliferation, reactive oxygen species and DNA damage of HepG2cellsand LO2cells under different concentration of DMNPs. The experiment results showed that in the presence of high concentration DMNPs, cell viability remained above70%. The morphology and production curve of cells was similar with the negative control. The hemolysis and stability test also indicated that the DMNP had good biological compatibility.2) The interaction study between DMNPs and cells by SEM and TEM showed that the DMNP was uptake in cell by phagocytosis, and localized in the cell inner matrix. The detection of reactive oxidative species implied that the cytotoxicity was relative to the oxidative stress.3) Cytotoxicity of Doxrobincin-loaded magnetic particles was evaluated in vitro by the HepG2and EC cell. The results showed that the IC5o of Dox was1.34mg/mL, while the IC50of DOX-DMNPs was1.98mg/mL, showing lower cytotoxicity. The ROS detection results indicated the ROS concentration of Doxrobincin-loaded magnetic particles was also lower than that of Dox. In the same concentration of Dox, HepG2cells showed more sensitive than EC cells.Overall, dextran magnetic composite particles have good biocompatibility in in vitro assessment, which have the promising application as magnetic drug carrier in the targeted therapy.