Relationship Between Characters Of Gold Nanoparticles And Their Cellular Biological Effects

The safety of nanomaterials has drawn highly attention for its promising biomedical applications.Biological effects of nanomaterials are widely influenced by characters of nanomaterials such as size,shape,surface modification,etc.Researches were mostly focused on size,surface modification of nanoparticles and their cytotoxicity.Few researchers have pay much attention to dispersity of nanoparticles.Furthermore,the autophagy playing a key role in human health and disease has become a hot research subject.Therefore,to investigate the relationship between characters of nanoparticles and their induced autophagy could guild the fabrication and application of nanoparticles.In this thesis,we chosed gold nanoparticles with the controllable size and shape and good biocompatibility as an example and explored the relationship between their physio-chemical properties(size,morphology,surface modification&dispersity)and their autophagic effect.The main points are presented as follows.Chapter 1 we briefly summarized the properties of nanomaterials and the development of researches in cytotoxicity and autophagy.In addition,the main idea and the objectives of this thesis are proposed.Chapter 2 we investigated the effect of dispersity of nanoparticles on their cytotoxicity.We synthesized 12 nm Au @ DMSA nanoparticles and mixed them with culture medium quickly or slowly to adjust the dispersity of gold nanoparticles.Our data indicated that the cytotoxicity of aggregated gold nanoparticles is significantly higher than well-dispersed ones.The dispersity-dependent cytotoxicity may be related to the increase of cellular endocytosis and reactive oxygen species.Chapter 3 we explored the relationship between four Au nanoparticles with different characters and their autophagic effect.We incubated two gold nanopa rticles groups which have different shape but same volume with HeLa cells tha t stably express GFP-LC3.We showed that Au Sphere @ Citrate induced significa nt autophagic level in comparison with Au Rod.Chapter 4 we explored the mechanism of gold nanoparticles induced autop hagic effect.Through TEM images and immunofluorescence of cells,we found that the intracellular gold nanoparticles were located in lysosome.By calculating 1 ysosome number and size,detecting the depolarization of mitochondria,we fou nd that gold nanoparticles would cause Lysosome enlargement and impairment.Gold nanoparticles could impair lysosome degradation capacity and induce autoph agosome accumulation.