表面改性对纳米材料穿透细胞膜能力的影响及机理表征

With the development of nanotechnology and its advances in interdisciplinary research, nanomaterials have received increasing attention due to their great potential applications in biomedical sciences. Taking advantage of the unique size-dependent properties and surface effect, the biological behavior of nanomaterials can be effectively manipulated by smart surface functionalization, which has opened new avenues exploring their use in the fields of specific targeting, drug delivery, and enhanced bioimaging. This proposal focuses on the effect of surface functionalization on the penetration of nanomaterials with different geometries across a cell membrane. The principles and mechanisms of surface functionalization on the penetration of nanomaterials are revealed by coarse-grained molecule dynamics simulations and application of thermodynamic integration method to nano-biological systems. Bioimaging experiments will be carried out for verifications of the revealed mechanisms. The investigations on the mechanism of surface functionalization for nanomaterials with different geometries are critical to manipulation and safe design of nanomaterial-enabled biological applications.

随着纳米科技的兴起和学科间交叉融合，人们对纳米材料在生物系统中的应用给予了广泛的国际关注。利用纳米材料独特的尺寸效应和表面效应，通过智能修饰纳米材料的表面性质，能够显著改变纳米材料的生物靶向、药物输运及增强生物成像的能力。该申请旨在采用粗粒化分子动力学模型，并结合在纳米生物系统中应用热力学积分方法，研究表面改性对不同几何特征的纳米材料穿透细胞膜进入细胞的动态过程的影响，揭示表面改性影响纳米材料穿透细胞膜的规律与机制，并借助生物成像实验对所揭示的机理予以验证。本项课题研究将为纳米材料生物效应的控制和功能化设计提供一定的理论依据。

该项目聚焦了纳米材料与细胞膜接触作用的生物行为，利用粗粒化分子动力学模型揭示了多种形状的纳米衍生结构与细胞膜接触的全动力学过程，系统研究了表面亲疏水改性调控不同几何形状纳米材料穿膜行为的规律，并从理论上阐明了这一过程的关键力学控制变量，完善了不同几何形状纳米材料生物传质模式的研究体系。此外，还研究了表面亲疏水改性对柔性纳米颗粒穿透细胞膜能力的影响，揭示了表面改性与刚度耦合影响纳米颗粒传质效率的力学机制。并拓展研究了表面改性影响二维纳米材料面内强度和导热性能的规律和机理，实现了石墨烯力热性能的表面氢化改性调控。该项目研究进展对纳米低维材料的生物毒性以及纳米结构的靶向药物输运具有重要意义，项目研究结果在微纳米研究领域的重要刊物Nanoscale、Carbon等刊物发表SCI论文12篇，参加国内外学术会议12次，其中国际会议7次，所发表的工作也获得了很好的学界评价。项目研究培养毕业硕士生1人，另有在读硕士生3人，并辅助培养1名博士生和1名硕士生。