ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.
ACS Nano. 2021 Jun 22;15(6):10025-10038. doi: 10.1021/acsnano.1c01642. Epub 2021 May 19.
Poly(ethylene glycol) (PEG) is widely used in particle assembly to impart biocompatibility and stealth-like properties for diverse biomedical applications. Previous studies have examined the effect of PEG molecular weight and PEG coating density on the biological fate of various particles; however, there are few studies that detail the fundamental role of PEG molecular architecture in particle engineering and bio-nano interactions. Herein, we engineered PEG particles using a mesoporous silica (MS) templating method and investigated how the PEG building block architecture impacted the physicochemical properties (, surface chemistry and mechanical characteristics) of the PEG particles and subsequently modulated particle-immune cell interactions in human blood. Varying the PEG architecture from 3-arm to 4-arm, 6-arm, and 8-arm generated PEG particles with a denser, stiffer structure, with increasing elastic modulus from 1.5 to 14.9 kPa, inducing an increasing level of immune cell association (from 15% for 3-arm to 45% for 8-arm) with monocytes. In contrast, the precursor PEG particles with the template intact (MS@PEG) were stiffer and generally displayed higher levels of immune cell association but showed the opposite trend-immune cell association decreased with increasing PEG arm numbers. Proteomics analysis demonstrated that the biomolecular corona that formed on the PEG particles minimally influenced particle-immune cell interactions, whereas the MS@PEG particle-cell interactions correlated with the composition of the corona that was abundant in histidine-rich glycoproteins. Our work highlights the role of PEG architecture in the design of stealth PEG-based particles, thus providing a link between the synthetic nature of particles and their biological behavior in blood.
聚乙二醇（PEG）广泛用于颗粒组装，以赋予各种生物医学应用的生物相容性和类似隐身的特性。以前的研究已经研究了 PEG 分子量和 PEG 涂层密度对各种颗粒的生物命运的影响；然而，很少有研究详细描述 PEG 分子结构在颗粒工程和生物纳米相互作用中的基本作用。在此，我们使用介孔硅（MS）模板法设计了 PEG 颗粒，并研究了 PEG 构建块结构如何影响 PEG 颗粒的物理化学性质（表面化学和机械特性），并随后调节人血中颗粒与免疫细胞的相互作用。改变 PEG 结构从 3 臂到 4 臂、6 臂和 8 臂，生成了具有更密集、更刚性结构的 PEG 颗粒，弹性模量从 1.5 增加到 14.9 kPa，诱导免疫细胞与单核细胞的结合水平增加（从 3 臂的 15%增加到 8 臂的 45%）。相比之下，具有完整模板的 PEG 前体颗粒（MS@PEG）更硬，通常显示更高水平的免疫细胞结合，但表现出相反的趋势-随着 PEG 臂数量的增加，免疫细胞结合减少。蛋白质组学分析表明，形成在 PEG 颗粒上的生物分子冠对颗粒与免疫细胞的相互作用的影响最小，而 MS@PEG 颗粒与细胞的相互作用与富含组氨酸糖蛋白的冠的组成相关。我们的工作强调了 PEG 结构在设计隐形 PEG 基颗粒中的作用，从而在颗粒的合成性质与其在血液中的生物学行为之间建立了联系。
