Department of Chemical Engineering, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
College of Engineering, Michigan State University, East Lansing, MI 48824, United States.
J Colloid Interface Sci. 2017 Oct 15;504:325-333. doi: 10.1016/j.jcis.2017.05.046. Epub 2017 May 18.
PEGylation on nanoparticles (NPs) is widely used to prevent aggregation and to mask NPs from the fast clearance system in the body. Understanding the molecular details of the PEG layer could facilitate rational design of PEGylated NPs that maximize their solubility and stealth ability without significantly compromising the targeting efficiency and cellular uptake. Here, we use molecular dynamics (MD) simulation to understand the structural and dynamic the PEG coating of mixed monolayer gold NPs. Specifically, we modeled gold NPs with PEG grafting densities ranging from 0-2.76chain/nm, chain length with 0-10 PEG monomers, NP core diameter from 5nm to 500nm. It is found that the area accessed by individual PEG chains gradually transits from a "mushroom" to a "brush" conformation as NP surface curvature become flatter, whereas such a transition is not evident on small NPs when grafting density increases. It is shown that moderate grafting density (∼1.0chain/nm) and short chain length are sufficient enough to prevent NPs from aggregating in an aqueous medium. The effect of grafting density on solubility is also validated by dynamic light scattering measurements of PEGylated 5nm gold NPs. With respect to the shielding ability, simulations predict that increase either grafting density, chain length, or NP diameter will reduce the accessibility of the protected content to a certain size molecule. Interestingly, reducing NP surface curvature is estimated to be most effective in promoting shielding ability. For shielding against small molecules, increasing PEG grafting density is more effective than increasing chain length. A simple model that includes these three investigated parameters is developed based on the simulations to roughly estimate the shielding ability of the PEG layer with respect to molecules of different sizes. The findings can help expand our current understanding of the PEG layer and guide rational design of PEGylated gold NPs for a particular application by tuning the PEG grafting density, chain length, and particle size.
聚乙二醇（PEG）化纳米颗粒（NPs）广泛用于防止聚集，并使 NPs 从体内快速清除系统中隐匿。了解 PEG 层的分子细节可以促进合理设计 PEG 化 NPs，使其在不显著降低靶向效率和细胞摄取的情况下，最大限度地提高其溶解度和隐身能力。在这里，我们使用分子动力学（MD）模拟来理解混合单层金 NPs 的 PEG 涂层的结构和动态。具体来说，我们模拟了 PEG 接枝密度范围为 0-2.76 链/纳米、链长为 0-10 PEG 单体、NP 核直径为 5nm 至 500nm 的金 NPs。结果发现，随着 NP 表面曲率变得更加平坦，单个 PEG 链的可及面积逐渐从“蘑菇”构象过渡到“刷”构象，而在接枝密度增加时，这种转变在小 NP 上并不明显。结果表明，适度的接枝密度（约 1.0 链/纳米）和短链长足以防止 NPs 在水介质中聚集。通过动态光散射测量 PEG 化 5nm 金 NPs，验证了接枝密度对溶解度的影响。就屏蔽能力而言，模拟预测增加接枝密度、链长或 NP 直径都会降低受保护内容物对一定大小分子的可及性。有趣的是，降低 NP 表面曲率估计是提高屏蔽能力最有效的方法。对于屏蔽小分子，增加 PEG 接枝密度比增加链长更有效。根据模拟结果，开发了一个包含这三个研究参数的简单模型，以粗略估计 PEG 层对不同大小分子的屏蔽能力。这些发现有助于扩展我们对 PEG 层的现有认识，并通过调整 PEG 接枝密度、链长和颗粒大小来指导针对特定应用的 PEG 化金 NPs 的合理设计。
