Lee Hwankyu
Department of Chemical Engineering, Dankook University, Yongin-si 16890, Korea.
Pharmaceutics. 2021 Apr 29;13(5):637. doi: 10.3390/pharmaceutics13050637.
The conformations and surface properties of nanoparticles have been modified to improve the efficiency of drug delivery. However, when nanoparticles flow through the bloodstream, they interact with various plasma proteins, leading to the formation of protein layers on the nanoparticle surface, called protein corona. Experiments have shown that protein corona modulates nanoparticle size, shape, and surface properties and, thus, influence the aggregation of nanoparticles and their interactions with cell membranes, which can increases or decreases the delivery efficiency. To complement these experimental findings and understand atomic-level phenomena that cannot be captured by experiments, molecular dynamics (MD) simulations have been performed for the past decade. Here, we aim to review the critical role of MD simulations to understand (1) the conformation, binding site, and strength of plasma proteins that are adsorbed onto nanoparticle surfaces, (2) the competitive adsorption and desorption of plasma proteins on nanoparticle surfaces, and (3) the interactions between protein-coated nanoparticles and cell membranes. MD simulations have successfully predicted the competitive binding and conformation of protein corona and its effect on the nanoparticle-nanoparticle and nanoparticle-membrane interactions. In particular, simulations have uncovered the mechanism regarding the competitive adsorption and desorption of plasma proteins, which helps to explain the Vroman effect. Overall, these findings indicate that simulations can now provide predications in excellent agreement with experimental observations as well as atomic-scale insights into protein corona formation and interactions.
纳米颗粒的构象和表面性质已被修饰以提高药物递送效率。然而，当纳米颗粒在血液中流动时，它们会与各种血浆蛋白相互作用，导致在纳米颗粒表面形成蛋白质层，称为蛋白质冠。实验表明，蛋白质冠会调节纳米颗粒的大小、形状和表面性质，从而影响纳米颗粒的聚集及其与细胞膜的相互作用，这可能会提高或降低递送效率。为了补充这些实验结果并理解实验无法捕捉的原子水平现象，在过去十年中进行了分子动力学（MD）模拟。在这里，我们旨在综述MD模拟在理解以下方面的关键作用：（1）吸附在纳米颗粒表面的血浆蛋白的构象、结合位点和强度；（2）血浆蛋白在纳米颗粒表面的竞争性吸附和解吸；（3）蛋白质包被的纳米颗粒与细胞膜之间的相互作用。MD模拟成功地预测了蛋白质冠的竞争性结合和构象及其对纳米颗粒-纳米颗粒和纳米颗粒-膜相互作用的影响。特别是，模拟揭示了血浆蛋白竞争性吸附和解吸的机制，这有助于解释弗罗因德效应。总体而言，这些发现表明，模拟现在可以提供与实验观察结果高度一致且关于蛋白质冠形成和相互作用的原子尺度见解的预测。
