细胞内吞纳米颗粒药物的数值模拟研究

A NUMERICAL STUDY ON ENDOCYTOSIS OF NANOPARTICLES

受体介导的内吞是细胞与外界物质交换的常见方式.采用配体修饰表面的纳米脂质体颗粒,将药物有针对性地投放到肿瘤细胞以提高药物传输的效率,是药物传输系统设计中的核心问题之一.本文假设内吞是准静态过程,采用三维数学模型来模拟球状纳米颗粒的内吞,建立了包含绑定键的系统变形能方程,通过求解能量方程的最小值,得到药物在每个内吞包裹阶段的变形以及药物的被动内吞所需最小能量,分析不同药物半径对内吞所需最小能量的影响.研究表明,细胞膜变形能与绑定键变形能占总能量的绝大部分,各组分随着包裹区域增加均有变化;在给定细胞膜和药物颗粒的硬度、绑定键强度等物理特性下存在最优药物尺寸,使得内吞过程中总能耗最小;在药物内吞进行的后期,包裹区域边缘的绑定键因伸长过大发生断裂,影响内吞的顺利完成.本研究为受体介导的高效药物设计提供了理论支撑.

Receptor-mediated endocytosis is one of the means for cells to exchange materials with their environments.Vesicles coated with ligands on their surface are often adopted for the drug delivery in cancer therapy through receptor-mediated endocytosis as well.In the present work,we used a 3D mathematical model and energy minimization to study the endocytosis process of spherical drug nanoparticles.The total energy of the system including catch bonds was established.The minimization of the energy functional was carried out numerically.The shape of particle and cell membrane in each wrapping stage was obtained,and the influence of particle size on the minimum energy required for passive endocytosis was analysed.The results show that cell membrane and receptor-ligand bonds deformation energies are the major components of the total deformation energy,and each component changes as the wrapping area is increased.There exists an optimal size of nanoparticles for which the total energy consumption is minimum under given membrane stiffness and receptor-ligand bond strength.We also found that at the final stage of wrapping the endocytosis may not be completed because of the breaking of overstretched receptor-ligand bonds.This study provides a theoretical insight for the design of receptor mediated high efficiency drug delivery system.