Evaluation Of Zn_0.4Fe_2.6O₄Nanoparticle Toxicity In Mice

Numerous investigations on various types of iron oxides have been carried out in the field of magnetic nanomaterials, such as maghemite, y-Fe2O3, and magnetite, Fe3O4, among which magnetite is a very potential candidate because of its biocompatibility. Superparamagnetic iron oxide nanoparticles (SIONPs) offer many applications in biomedicine such as bioimaging, targeted drug delivery, biosensors, anticancer hyperthermia therapy, tissue repair, and cell sorting mainly owing to their good chemical stability and magnetic responsiveness, in addition to possessing the general characteristics of nanoparticles. Anticancer drugs can be transported through the vascular system and specifically target to the tumor site using SPIONs as drug delivery systems with the aid of a magnetic field, reducing the damage of healthy cells. Sufficient magnetic susceptibility is essential for effective utilization of magnetic force to ensure the transport of the drug carrier to the target site before release. Zn2+doped SIONPs possess higher magnetic susceptibility than that of conventional SIONPs. Therefore, Zn2+doped SIONPs as drug carriers and imaging contrast agents are significantly superior to that of conventional SIONPs.SIONPs, as diagnostic and therapeutic agent, can be delivered by the intravenous route; besides, they are also a favorable candidate as oral delivery of therapeutic agents and MRI contrast agents for the gastrointestinal tract. Compared to the parenteral route of administration, oral administration can improve patient compliance and comfort. Furthermore, oral cavity is a vital portal of entry of nanomaterials from the environment into human body. Such as,SPIONs can be ingested directly via water, food, cosmetics, drugs, drug delivery devices, etc. Therefore, it is critical to assess the toxicity of Zn2+doped SIONPs by oral administration. In this paper, we determined the oral toxicity of Zno.4Fe2.6O4NPs in mice. The whole thesis is divided into four chapters.The first chapter:It is a brief review of nanomaterials, their way of invasion and biological toxicity. We also introduce the magnetic properties of the IONPS and its wide applications in biomedical field. Finally, we summarize the toxic mechanism of IONPS and the properties affected by the in vitro toxicity, route of administration and target organ toxicity in vivo.The second chapter:We have synthesized Zn0.4Fe2.6O4NPs by hydrothermal method. The characterizations of nanoparticles’phase, shape and size, elemental analysis, surface modification and magnetic properties were carried out by XRD、TEM、EDS、ICP-AES、FTIR、SQUID. After repeated intragastric administration of Zn0.4Fe2.6O4NPs for one month, significant increases in Fe and Zn contents were found in the liver, kidney, spleen, lung, small intestine and stomach of mice compared to the control. No significant changes in Fe and Zn contents were observed for the brain and heart. After repeated intragastric administration of Zn0.4Fe2.6O4NPs for one month, no significant differences were observed in body weights, coefficients of organs, histopathological and ultrastructural of tissues, daily activity and symptoms of the mice between the control and experimental groups. These results indicated that Zn0.4Fe2.6O4NPs didn’t induce obvious toxicity in mice.The third chapter:We have assessed the effect of Zn0.4Fe2.6O4NPs on the functions of liver and kidney of mice by assaying oxidative stress and serum biochemical parameters. The results of enzyme activity assay showed that Zn0.4Fe2.6O4NPs induced the slight oxidative stress in the liver and kidney of mice compared to the control. Based on the result of biochemical markers of liver and kidney, we deduced that this slight oxidative stress did not seem to be high enough to impair their functions and could be successfully counteracted by their intrinsic antioxidant systems.The fourth chapter:The stability of Zn0.4Fe2.6O4NPs has been analyzed in artificial gastrointestinal fluid, artificial intestinal fluid and artificial blood solution. The nearly insoluble property of Zn0.4Fe2.6O4NPs in artificial gastrointestinal fluid, artificial intestinal fluid and artificial blood solution indicated that the stability of Fe3O4NPs was significantly enhanced by Zn2+doping, which may play another role in attenuating Fe3O4NPs toxicity in mice by decreasing the amount of metal ion release from nanoparticles. Besides, we speculated that intact Zn0.4Fe2.6O4NPs may pass though the intestinal membrane into the blood circulation system by evaluating the DLS of nanoparticles in artificial intestinal fluid and artificial blood solution, and the magnetic property in the spleen.