针对应用安全性的无机生物医用纳米材料的细胞毒性及其分子机制研究

The inorganic nanomaterials including oxides, sulfides, selenides, calcium phosphates and calcium carbonate exhibited important application potentials in different biomedical fields, such as the biological florescent labeling, bone repair and drug delivery. However, the studies of the possible cytotoxic effects of these materials on human cells and the corresponding molecular biological mechanism are seldom, which results in the serious application safety risk. In this project, the biological molecules without potential cytotoxicity including vitamins, proteins and polysaccharides will be used as the matrices to regulate the preparation of the above-mentioned representative inorganic nanomaterials with different physico-chemical properties. The studies will be performed from three aspects. Firstly, the regulation effects of the preparation methods, preparation conditions, and structures of biomolecules on the physico-chemical properties of the materials will be studied in detail. Secondly, based on various cellular biological and molecular biological methods, the potential cytotoxicities of these materials on different human cells will be studied. Thirdly, the relationship between the physico-chemical properties of the materials and the cytotoxicities will be systematically explored from the cellular and molecular levels. The important factors affecting the cytotoxicities of the materials and the corresponding molecular biological mechanism will be discovered. The results are highly instructive to the improvement of the application safety, purposiveness and effectiveness of the inorganic biomedical nanomaterials in different biomedical fields. Moreover, these results can develop the strong theoretical and laboratory bases for the design and preparation of the novel biomedical materials.

氧化物、硫（硒）化物、钙磷酸盐、碳酸钙等无机纳米材料在生物荧光标记、人骨修复、药物传输等生物医学领域具有广阔的应用前景。然而目前针对这些材料可能对人体细胞产生的毒性作用及相应的分子机制尚缺乏系统深入的研究，存在严重的应用安全风险。本项目拟选择组成和显微结构有代表性的上述无机纳米材料，以维生素、蛋白质、多糖等生物分子为有机基质调控系列无机纳米材料的合成并开展以下三方面的研究。一是研究合成方法、合成条件和生物分子结构对材料理化性质的调控规律；二是综合运用多种细胞分子生物学手段从细胞和分子层次上研究上述材料对系列人体细胞所产生的毒性作用；三是研究材料理化性质与其细胞毒性之间的相互关系并确定影响细胞毒性作用的关键因素，最终揭示其分子生物学机制。研究结果对提高无机生物医用纳米材料在生物医学领域的应用安全性、目的性和有效性具有重要的指导意义，同时可为开发新型生物医用材料提供坚实的理论基础和实验依据。