Donadoni Edoardo, Siani Paulo, Gambari Simone, Campi Davide, Frigerio Giulia, Di Valentin Cristiana
Department of Materials Science, University of Milano-Bicocca, Via R. Cozzi 55, Milano 20125, Italy.
BioNanoMedicine Center NANOMIB, University of Milano-Bicocca, Milano 20125, Italy.
ACS Appl Mater Interfaces. 2025 Apr 2;17(13):19304-19316. doi: 10.1021/acsami.4c21303. Epub 2025 Mar 24.
Nanodiamonds (NDs) have emerged as potential candidates for versatile platforms in nanomedicine, offering unique properties that enhance their utility in drug delivery, imaging, and therapeutic applications. To improve their biocompatibility and nanomedical applicability, NDs are coated with organic polymer chains, such as poly(ethylene glycol) (PEG), which are well known to prolong their blood-circulating lifetime by reducing the surface adsorption of serum proteins. Theoretical simulations are useful tools to define, at the atomic level, the optimal parameters that guide the presentation of the coating chains in the biological environment and the interaction of coated NDs with proteins. In this work, we perform atomistic molecular dynamics (MD) simulations of several PEGylated spherical ND models immersed in a realistic physiological medium. In particular, we evaluate the effect of the polymer chain's terminal group, length, grafting density, and the ND core dimension on both the structural properties of the PEG coating and the interaction of the nanoconjugates with the aqueous phase. Moreover, we investigate the role played by the chemical nature of the core material through a comparative analysis with a PEGylated spherical titanium dioxide (TiO) nanoparticle (NP). Among all the parameters evaluated, we find that the PEG grafting density, the PEG chain length, and the NP core material are key factors in determining the dynamic behavior of PEGylated nanosystems in solution, whereas the PEG terminal group and the ND dimension only play a marginal role. These factors can be strategically adjusted to identify the optimal conditions for enhanced clinical performance. Finally, we prove that the PEG coating prevents the aggregation of two ND particles. We believe that this computational study will provide valuable insights to the experimental community, supporting the rational design of polymer-coated inorganic NPs for more efficient nanomedical applications.
纳米金刚石（NDs）已成为纳米医学中多功能平台的潜在候选者，具有独特的性质，可增强其在药物递送、成像和治疗应用中的效用。为了提高其生物相容性和纳米医学适用性，NDs 被有机聚合物链包覆，如聚乙二醇（PEG），众所周知，PEG 可通过减少血清蛋白的表面吸附来延长其血液循环寿命。理论模拟是在原子水平上定义指导涂层链在生物环境中呈现以及包覆 NDs 与蛋白质相互作用的最佳参数的有用工具。在这项工作中，我们对浸没在真实生理介质中的几种聚乙二醇化球形 ND 模型进行了原子分子动力学（MD）模拟。特别是，我们评估了聚合物链的端基、长度、接枝密度以及 ND 核心尺寸对 PEG 涂层结构性质和纳米缀合物与水相相互作用的影响。此外，我们通过与聚乙二醇化球形二氧化钛（TiO）纳米颗粒（NP）的对比分析，研究了核心材料化学性质所起的作用。在所有评估的参数中，我们发现 PEG 接枝密度、PEG 链长度和 NP 核心材料是决定聚乙二醇化纳米系统在溶液中动态行为的关键因素，而 PEG 端基和 ND 尺寸仅起次要作用。这些因素可以进行策略性调整，以确定增强临床性能的最佳条件。最后，我们证明 PEG 涂层可防止两个 ND 颗粒聚集。我们相信这项计算研究将为实验界提供有价值的见解，支持为更高效的纳米医学应用合理设计聚合物包覆的无机 NPs。
