Research Of The Mechanism Of The Cancer Cellular Toxicity Of Magnetic Iron-oxide Nanoparticles

Cancer has become a severe threat of human health.Now there are many ways to treat with cancer,including magnetic nanoparticles.Magnetic nanomaterials can be used in therapy as well as diagnosis,so it is very important to clarify their cellular toxicity.We have developed a novel way to synthesize magnetic Fe3O4 nanoparticles with PLGA cover,which is IO-PLGA nanoparticles,to do research on its cellular toxicity.In this investigation,we have investigated the characteristics of the nanoparticles and done research on their cellular toxicity for different organelles.The raw material is Fe(acac)3,we use solvent-free dissolving method in making the nanoparticles.We should heat the system to a relatively high temperature with the protection of Argon flow,and then wash the nanoparticles with alcohol to get IO-NPs.Through seeding repeatedly,we can get nanoparticles in different diameters,from 7 nm to 15 nm.That means we can modulate the size of nanoparticle in a certain range.Moreover,we have determined their magnetic character through magnetic body.Then we should cover them with PLGA to get IO-PLGA nanoparticles.The characteristics of the nanoparticles are that their sizes are 203.2±5.2 nm and their surface zeta electrons are-22.6±1.4 mV.After doing the investigation about the cellular toxicity of the IO-NPs,we find that the existence of IO-NPs will be detrimental to cells while the PLGA-covered IO-NPs will be much milder for the cells.Thus we started to investigate the cellular toxicity of IO-NPs in autophagy.The result shows that the nanoparticles will be absorbed by endosome.From early-endosome to late-endosome,and finally the nanoparticles reach lysosome.The damage of lysosome,mitochondrial,ER and Golgi's complexes caused by the nanoparticles will enhance the autophagy level of the cells,which will lead to cell death.After the animal experiment,we can find that the mice with IO-NPs show enhanced autophagy in spleen and kidney cells,which mean that IO-NPs are somewhat toxic for mice.However,the PLGA-covered nanoparticles are much less toxic than bare nanoparticles.Therefore,we can conclude that the PLGA cover can significantly decrease the cellular toxicity of magnetic iron-oxide nanoparticles.