Lunnoo Thodsaphon, Assawakhajornsak Jirawat, Ruangchai Sukhum, Puangmali Theerapong
Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand.
Department of Physics, King's College London, Strand, London, WC2R 2LS, United Kingdom.
J Phys Chem B. 2020 Mar 12;124(10):1898-1908. doi: 10.1021/acs.jpcb.9b11600. Epub 2020 Feb 21.
A surface modification of nanoparticles (NPs) provides an effective way to control their interactions with living cells. The complete understanding of interactions between NPs and a cell membrane is a key step for the development of drug delivery. In the present work, the role of different surface charges (anionic, cationic, and zwitterionic) on the internalization through an idealized plasma membrane was investigated using a coarse-grained molecular dynamics (CGMD) technique. The decorated AuNPs used in this study closely imitated those experimentally synthesized, while the idealized plasma membrane model resembled that found in living cells. The mechanism of direct translocation of a 2 nm particle by membrane was observed. The zwitterionic AuNP demonstrates a higher free-energy barrier than the positively and negatively charged AuNPs, resulting in a lack of preference for internalization across the membrane, leading to lower translocation rate and permeability of internalization. Despite the surface coverage, the agglomeration of AuNPs in a physiological condition has been observed resulting in slow unfavorable permeability. Our study highlights that in addition to surface charges, the hydrodynamic size () plays an important role in the permeability of the functionalized AuNPs into the cell membrane. Through our simulations, complete understanding of interactions between ligands-coated AuNPs and the realistic plasma membrane has been established serving as a platform for the novel design of AuNPs in nanomedicine applications.
纳米颗粒（NPs）的表面修饰为控制其与活细胞的相互作用提供了一种有效方法。全面了解NPs与细胞膜之间的相互作用是药物递送发展的关键一步。在本工作中，使用粗粒度分子动力学（CGMD）技术研究了不同表面电荷（阴离子、阳离子和两性离子）对通过理想化质膜内化的作用。本研究中使用的修饰金纳米颗粒（AuNPs）与实验合成的颗粒非常相似，而理想化的质膜模型类似于活细胞中的质膜。观察到2纳米颗粒通过膜直接转运的机制。两性离子AuNP表现出比带正电和带负电的AuNPs更高的自由能垒，导致对跨膜内化缺乏偏好，从而导致更低的转运速率和内化渗透率。尽管有表面覆盖，但在生理条件下仍观察到AuNPs的团聚，导致缓慢且不利的渗透率。我们的研究强调，除了表面电荷外，流体动力学尺寸（）在功能化AuNPs进入细胞膜的渗透率中也起着重要作用。通过我们的模拟，已经建立了对配体包被的AuNPs与实际质膜之间相互作用的全面理解，为纳米医学应用中AuNPs的新型设计提供了一个平台。
