Biotransformation And Metabolism Of Superparamagnetic Iron Oxide Nanoparticles In Mice

With nanoscience and nanotechnology developing rapidly, more and more engineered nanomaterials (ENMs) are applied to various fields of people’s daily life. Superparamagnetic iron oxide nanoparticles (SPIONs) are universally used in nano biomedical gradually due to their superparamagnetism, as the contrast agent of magnetic resonance imaging (MRI) and targeting drug carrier, and they can also be applied to the tumor magnetic heat treatment, genetic engineering and histologic study. However, the metabolic behaviors of SPIONs after entering the human body are still lack of knowledge, limiting their further application.This study does detailed characterization of two independent synthetic SPIONs with the sizes of 6 nm and 55 nm, evaluates their toxicity to target organs, observes the distribution of SPIONs with isotope tracer technique, and detects the disstribution and transformation with transmission electron microscopy (TEM) and synchrotron radiation scanning transmission X-ray microscopy (STXM). The major results of our study are showed as follows:(1) The major target organs of SPIONs are liver and spleen, and SPIONs are enriched in the lysosomes of liver Kupffer cells and spleen macrophages. SPIONs in liver and spleen cause varying degrees of oxidative damage in the short term, but their toxicities can be recovered at 7 day after injection, and there is no obvious physical damage in both of the two groups.(2) The metabolic ways of two kinds of radiolabeled SPIONs (64Cu and 59Fe) are similar, mainly excreting from body with the feces, secondly with urine. The radiolabeled SPIONs are quickly cleared from blood in about 30 min after injection, while the clearance of ions is relatively slow and inefficient. Colchicine can inhibit the excretion of lysosome, inducing the inhibition of the liver-gallbladder-intestines metabolic pathways, so the radioactive content in feces decreases, which give the evidence of the metabolic pathways.(3) The dissolution of SPIONs in phagolysosome simulant fluid (PSF) is quite fast, which indicates the iron in metabolic product is in the form of ions. The result of STXM indicated there are some ferritins arround the lysosomes which contains a large number of SPIONs in macrophage. Some of the degraded SPIONs can be involved in the process of iron metabolism in vivo by combining with ferritins.This research discusses the relation between the physical-chemical properties of the two size SPIONs and their biological effect. Combining traditional method with sotope tracer technique and synchrotron radiation to study the biotransformation and metabolism mechanism, it is clear that SPIONs can induce a short oxidative stress which will recover in a few days, and some of the degraded SPIONs in phagolysosome can combined with ferritins and involve in the process of iron metabolism. These results provide the important support for the drug safety of SPIONs in body test.