| Summary: | 碩士 === 國立中興大學 === 獸醫病理生物學研究所 === 99 === Nanoparticles are a relatively new class of biomedical products during the recent years. However, the small size and unique physicochemical properties of nanoparticles may cause their interactions with cellular components or proteins, and thus enter living cells. But until now, little has been known concerning the distribution and toxicity in the biological system. And the health risk is obviously related to the potential exposure of individuals to the nanoparticles. Silver nanoparticles are frequently used in consumer and medical products because of their effective antimicrobial activity. In this study, the average 7 nm-sized silver nanoparticles were synthesized with poly (styrene-co-maleic anhydrides, SMA) were conducted in vitro and in vivo methods to evaluate their biodistribution and safety. The SMA-AgNPs showed highly cytotoxicity on HepG2 cells. Moreover, hemolysis of murine erythrocytes was detected with these nanoparticles. For the in vivo study, SMA-AgNPs were administered to ICR mice via different pathways including intravenous (0.25, 0.5, and 1 mg/kg), intraperitoneal (1 mg/kg), intramuscular (0.25 and 1 mg/kg), and oral (1 mg/kg) routes. The mice after i.v. injection were sacrificed on day 1, 2, 3 and 7 after treatment. The other groups were sacrificed at day 7. Results show that SMA-AgNPs caused toxic signs such as dullness and paleness in i.v. 0.5 and 1 mg/kg groups and i.p. group within 3 days after treatment. Moreover, several mice were death. The increasing white blood cells, while erythrocytes, hemoglobin, hematocrit, and platelet were reducing. Grossly, livers became dark red and mottled. Spleens were enlarged gradually. Histologically, midzonal necrosis with telangiectasis in the liver and erythroid precursor cells hyperplasia in the spleen. And the silver nanoparticles mainly distributed to liver and spleen. After 7 days of treatment, the i.v. 0.5 mg/kg group showed slight inflammation in the liver, but massive necrosis in i.v. 1 mg/kg treated mice, and the silver particles also found in hepatocytes and kupffer cells. In addition, silver concentration also increased in the brain. Thus the median lethal dose (LD50) of SMA-AgNPs from i.v. injection is 0.78 mg/kg. Although, silver could be detected in various tissues via i.m. and oral treated groups, no toxic effect of SMA-AgNPs was found. These toxic variations might be related to the difference of treated pathways. In conclusion, it is suggested that liver and spleen are target organs of SMA-AgNPs, and SMA-AgNPs cause acute death to mice that may be related to its hepatic and hematological toxicities.
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