Department of Engineering Science and Mechanics, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
Nano Lett. 2013 Sep 11;13(9):4546-50. doi: 10.1021/nl402628n. Epub 2013 Aug 28.
Nanoparticles (NPs) hold great promises for targeted disease diagnosis and therapy. Despite considerable progress in biomimetic design of NP-bioconjugates, the roles of NP size and shape in endocytosis are still not fully understood. Using an efficient coarse-grained molecular dynamics (CGMD) model, we simulate receptor-mediated endocytosis of NPs of various sizes and shapes. Our simulations demonstrate that both NP size and shape modulate the kinetics of endocytosis. For spherical NPs, there exists an optimal size at which endocytosis takes the shortest time. For a spherocylindrical NP with the initial upright docking position on the membrane plane, endocytosis proceeds through a laying-down-then-standing-up sequence. A free energy analysis reveals that NP size primarily determines whether endocytosis can complete, while NP shape breaks the symmetry of curvature energy landscape and hence dictates the endocytic pathway and the angle of entry. The findings shed light on the rational design of NP-based diagnostic and therapeutic agents with improved cellular targeting.
纳米颗粒（NPs）在靶向疾病诊断和治疗方面具有巨大的应用前景。尽管在仿生设计的 NP-生物缀合物方面取得了相当大的进展，但 NP 大小和形状在胞吞作用中的作用仍未完全了解。本研究采用高效的粗粒化分子动力学（CGMD）模型，模拟了不同大小和形状的 NPs 的受体介导内吞作用。模拟结果表明，NP 的大小和形状都可以调节内吞作用的动力学。对于球形 NPs，存在一个最佳尺寸，使得内吞作用的时间最短。对于初始在膜平面上垂直停靠的球柱形 NP，内吞作用通过“躺下-然后站立”的顺序进行。自由能分析表明，NP 的大小主要决定了内吞作用是否能够完成，而 NP 的形状打破了曲率能量景观的对称性，从而决定了内吞途径和进入角度。这些发现为基于 NP 的诊断和治疗剂的合理设计提供了新的思路，以提高细胞靶向性。
