DNA在各向异性金属纳米探针不同晶面的行为机制及LSPR分析新方法研究

Metal nanoparticles have been widely used in biomedical analysis and imaging. However, the mechanism responsible for the interactions between biomolecules and crystal facets as well as the molecular recognition at biointerface is not clear yet, which limits our understanding on the biochemical analysis process and the improvement of analytical sensitivity, selectivity and reproducibility. The present proposal intends to systematically study the mechanism of the interactions between biomolecules (DNA as a typical case) and different facets on the surface of a metal nanocrystal, which can be fabricated on the basis of controlled synthesis technology and with anisotropic morphologies. By combining the theoretical simulations (e.g., density functional theory and molecular dynamics calculation) and experimental approaches (e.g., surface energy transfer, seed-mediated growth, and adsorption/desorption on crystal facets), we will investigate the influences of parameters such as structure, configuration, size, polarity, charge, and environmental medium on the interactions between DNA and metal nanocrystals. In addition to the mechanistic studies, we will also develop highly sensitive and real-time analytical methods for the detection of disease-related biomarkers and drugs. Understanding the scientific questions proposed here will enable us to complete the related theory as well as develop new methods for biomedical analysis and imaging. This project is both worth studying in theory and promising for practical applications.

金属纳米探针已广泛应用于生物医药分析及成像，但纳米探针的生物学界面效应及分子识别机制尚不清楚，使理解生化分析过程和提高分析灵敏度、选择性及重现性受到局限。本项目拟利用液相可控合成技术制备具有各向异性形貌和不同表面晶面的金属纳米晶来研究以DNA为代表的生物分子在金属纳米探针表面的行为机制。通过密度泛函理论、分子动力学等计算模拟方法和表面能量转移、晶种诱导生长、晶面吸附与解吸等实验手段深入探讨DNA结构、构象、尺寸、极性、电荷及环境介质等参数对二者相互作用的影响，提出作用规律及机理，并借以发展和建立面向重大疾病生物标志物和临床药物的高灵敏、实时分析法。项目凝练出如何阐明DNA在各向异性金属纳米探针不同晶面上的行为机制及其与分析灵敏度、选择性之间的内在联系这一关键科学问题，旨在完善金属纳米探针的生物界面效应及分子识别机制，并建立具有实际意义的生物医药分析和成像新方法，既有理论价值又有应用前景。

金属纳米探针已广泛应用于生物医药分析及成像研究，弄清分子与纳米探针表面的相互作用对构建相关分析方法学尤为重要。本项目以具有各向异性结构的金属纳米探针为研究对象，通过控制合成过程中的热力学和动力学因素，得到了多种形貌、尺寸和元素组成不同的金属纳米晶，进一步研究了DNA不同碱基与纳米晶特定晶面的相互作用，并将其应用于生化分析中。按照预期计划，项目取得了以下主要进展：. 1）制备了一系列具有各向异性结构、不同元素组成和局域表面等离子体共振（LSPR）性质的贵金属纳米晶，阐释了各向异性金属纳米探针的可控合成规律及特定晶面的形成机制，从而开发出有实际应用前景的新型LSPR纳米探针。. 2）探讨了DNA碱基与金属纳米探针特定晶面间的相互作用，通过实验手段明确了不同碱基与特定晶面之间结合能力的强弱、碱基附近的磷酸根对DNA在晶面上吸附的影响等，为前人的理论研究提供了实验数据支撑。. 3）以具有优异LSPR性质的各向异性金属纳米晶为分析探针，基于探针形貌结构、尺寸和元素定向改变诱导的LSPR信号变化，构建了一系列新型LSPR分析方法，并应用于生化样品的检测。