Abstract:
The most remarkable biomedical applications of nanoparticles (NPs) are in the diagnosis and treatment of various diseases. The promising future of gold nanoparticles (GNPs) in different biological applications has led to a strong interest in studying their possible deleterious effects in biological systems and how these effects might be mitigated. This thesis aimed to assess the biocompatibility of GNPs by using one or two doses of three different sizes of GNPs (5nm, 20nm and 50nm) and different exposure times (one or seven days) on liver, kidney and spleen of mice. Various molecular, biochemical, histological, immunohistochemical and transmission electron microscopy (TEM) approaches were used. The data analyzed by appropriate statistical methods. The results showed that small-sized GNPs (5nm) exerted an acute phase pro-inflammatory response in mice liver, which was subsided with time. In spleen, all sizes of GNPs significantly increased IL-1β and IL-6 expression on day 1 post dosing which persisted until day 7. In kidneys, none of the GNPs elicited a pro-inflammatory response; rather they insignificantly decreased the levels of pro-inflammatory cytokines expression. The priming dose of GNPs significantly inhibited the induction of acute phase immune response in GNP-treated mice. Immunostaining of cytokines showed similar observations. Biochemical analysis of markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) showed that GNPs did not significantly affect their levels in liver, kidney and spleen. The histopathology revealed that the size of GNPs plays an important role in their pathological effects on different organs of mice. The small sized GNPs preferentially targeted the liver whereas the medium and large size of GNPs significantly affected the spleen. There were minimal and insignificant pathological changes in kidneys irrespective of the GNPs size. The high magnification TEM images provided clear understanding of structural changed. In conclusion, the priming doses of GNPs significantly inhibited the acute phase immune responses in GNPs - treated mice, suggesting the importance of priming dose in nanmedicine applications. This strategy could have great potential in inhibiting the immune response and thus improving the bioavailability as well as biocompatibility of nanomaterials.
