基于功能化金纳米粒子的药物载体跨膜输运及生物毒性的介观模拟研究

Chemical products based on functionalized gold nanoparticles have broad application prospects in the field of biomedicine such as drug delivery; it is of great significance to deeply understand the interaction process and mechanism between functionalized gold nanoparticles and biomembranes in complex environments for developing related nanomedical products. Due to the complexity of biological systems, the microscopic interaction details between gold nanoparticles and biomembranes are still unclear. The project proposed here aims to study this international frontier research problem by means of computer molecular simulation. At first, under the framework of MARTINI coarse-grained force field, the theoretical model of biomembranes with complex components is constructed reasonably, and the structural characteristics and dynamic evolution process of multi-component biomembranes are explored on the mesoscopic scale. Then, based on the constructed reasonable biomembrane model, the interactions between biomembranes and functionalized gold nanoparticles with different physicochemical properties (surface charge properties, geometric shapes and surface characteristics) are systematically explored. Based on this, we expect to reveal the molecular mechanism of transmembrane transport and potential cytotoxicity of functionalized gold nanoparticles at the microscopic level, clarify the relationship between transmembrane efficiency and biotoxicity, and therefore provide significant theoretical guidelines for the development and application of biomedical gold nanomaterils with high efficiency and low toxicity.

基于功能化金纳米粒子的化工产品在生物医学领域如药物输运等具有广泛应用前景，深入理解其与生物膜在复杂环境下的相互作用过程及机理对相关纳米医用产品的开发应用具有重要意义。由于生物体系的复杂性，人们对功能化金纳米粒子与生物膜的微观作用细节目前仍然缺乏清晰的认识。本项目旨在通过计算机分子模拟方法针对这一国际前沿研究问题展开研究。首先在MARTINI粗粒化力场的基本框架下对具有复杂成分的生物膜进行理论模型的合理构建，在介尺度层面研究生物膜多组分的结构特性及其动态演化过程。基于得到的合理的生物膜模型，再采用介观粗粒化模拟方法系统性地考察其与不同物理化学性质（表面电荷性质、几何形状及表面结构特性）的金纳米粒子的界面相互作用，借此从微观水平上探究功能化金纳米粒子的跨膜输运行为及产生潜在细胞毒性的分子机制，明确其穿膜效率和生物毒性之间的关联性，为兼具高效性和低毒性的纳米金生物医用材料的开发应用提供理论指导。

从分子水平上理解纳米材料与细胞的相互作用在生物医学领域具有重要意义。本项目在MARTINI粗粒化力场的基本框架下对表面功能化金纳米粒子与细胞膜进行合理建模，利用分子动力学模拟从微观层面上研究了它们之间的相互作用和机制，其计算效率远高于传统的全原子分子动力学模拟方法，模拟结果也在很大程度上与相关实验吻合。研究表明，金纳米粒子表面的带电性质（带电符号和带电量）和疏水性质对其跨膜效率和潜在细胞毒性具有显著影响，生物膜自身的结构性质（曲率和流动性）也对相互作用具有重要影响。此外，我们也对本项目研究内容进行了有益扩展。这些研究成果在National Science Review，Small，Physical Chemistry Chemical Physics，Langmuir，Chinese Journal of Chemical Engineering等国际知名学术期刊上发表。本项目的研究结果对生物医学产品的研发指导具有一定的科学和实践意义。