Biosafety Of Typical Nanoparticles And PM_2.5from Combustion

In recent years,the wide use of nano-products,fossil fuel and biomass fuel has led to the increase of probability of people being exposed to particulate matter(PM).Engineered nanoparticles used in scientific research,industrial production and consuming products are hazardous to the researchers,workers and consumers.The inhalation of PM with the aerodynamic diameter less than 2.5 microns(PM2.5)and its deposition in lung could induce a variety of diseases.PM2.5 produced from burning of biomass straw is an important component of atmospheric particles in China which played an important role in the induction of toxic effect.The study of PM biosafety is of great significance for enhancing the awareness of PM safety.It will promote not only the development of toxicity inhibition methods but also the development of safety science.According to the exposure ways and applications of nanoparticles,we evaluated the biosafety and biotransformation of the typical nanoparticles(zinc oxide,dimercapto succinic acid coated zinc doping ferroferric oxide)under corresponding exposure ways.Under the exposure way of oral administration,the zinc oxide nanoparticles(nano ZnO)and ordinary zinc oxide showed similar toxic effect.Nano ZnO at the dose of 50 mg/kg showed mild toxic effect.However,co-exposure with dimethoate(DM),nano ZnO can significantly enhance the liver damage induced by DM.The accumulation of zinc and DM in liver cause obvious oxidative stress,resulting in liver damage.These results proved that ZnO has potential toxic effects in commodity application.Because of the good biocompatibility and wide biomedical applications of dimercapto succinic acid coated zinc doping ferroferric oxide(DMSA-Zn0.4Fe2 6O4),we studied the metabolic mechanism of it under oral administration.The results showed that although most of the nanoparticles were eliminated from the body by digestive system,there were still some nanoparticles that transited through small intestine in the form of complete particles,reached to spleen through blood circulation.Some of the particulate matters retained the original crystal structure in spleen,while some other particulate matter changed the crystal structure after binding with protein.The results indicated that DMSA-Zno aFe2.6O4 has the potential to be used as a drug carrier.Based on oral exposure study,we studied the biosafety of PM by inhalation.For inhalation exposure mode,we developed a(I)nose-only inhalation device for mice.Combining with an aerosol generator,we designed a PM aerosol exposure system.By applying this system,we evaluated the inhaled toxic effects of halloysite nanotubes(HNTs),a clay mineral dust in the atmosphere and also a typical nanomaterial that have wide applications.The results suggested that HNTs caused chronic toxicity and autophagy in mice.Most importantly,we found that it is possible to inhibit the toxicity of HNTs by applying trehalose through enhanced autophagy in mice.PM2.5 from biomass burning is the primary pollution sources in atmosphere and their toxic effects need further investigation.Based on(Ⅰ)nose-only inhalation device,we developed(Ⅱ)nose-only inhalation device which can realize exposure under multiple doses at the same time.By combining the self-developed biomass burning device,we designed an online exposure system for smoke produced by biomass burning.By applying the system,we evaluated the respiratory system toxicity induced by PM2.5 from wheat straw burning.The results indicated that PM2.5 entered the lung cells of mice and formed autophagosomes,leading to acute toxicity in lung.The composition and property of atmospheric PM2.5 is different from new born PM2.5,because atmospheric particles contain secondary components that have been aged.The cytotoxic experiment of PM2.5 sampled from atmosphere directly was then studied.After traditional water extraction,CH2Cl2 was used for the second extraction.The results confirmed that the second CH2Cl2 extracts were more toxic than H2O extracts.Incorporation of two extracts to treat cells can reflect real toxicity level and dosage.The work improved the traditional solution method for the study of PM2.5 toxic effect in cells and animals.This thesis emphasizes the importance to understand the biosafety of PM in every exposure way.This work will lay the foundations for comprehensively understanding the biological metabolism mechanism of nanoparticles and developing toxicity inhibition method.