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.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity , The University of Melbourne , Parkville , Victoria 3010 , Australia.
ACS Nano. 2019 May 28;13(5):4980-4991. doi: 10.1021/acsnano.9b00552. Epub 2019 Apr 18.
Upon exposure to human blood, nanoengineered particles interact with a multitude of plasma components, resulting in the formation of a biomolecular corona. This corona modulates downstream biological responses, including recognition by and association with human immune cells. Considerable research effort has been directed toward the design of materials that can demonstrate a low affinity for various proteins (low-fouling materials) and materials that can exhibit low association with human immune cells (stealth materials). An implicit assumption common to bio-nano research is that nanoengineered particles that are low-fouling will also exhibit stealth. Herein, we investigated the link between the low-fouling properties of a particle and its propensity for stealth in whole human blood. High-fouling mesoporous silica (MS) particles and low-fouling zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) particles were synthesized, and their interaction with blood components was assessed before and after precoating with serum albumin, immunoglobulin G, or complement protein C1q. We performed an in-depth proteomics characterization of the biomolecular corona that both identifies specific proteins and measures their relative abundance. This was compared with observations from a whole blood association assay that identified with which cell type each particle system associates. PMPC-based particles displayed reduced association both with cells and with serum proteins compared with MS-based particles. Furthermore, the enrichment of specific proteins within the biomolecular corona was found to correlate with association with specific cell types. This study demonstrates how the low-fouling properties of a material are indicative of its stealth with respect to immune cell association.
当纳米工程颗粒暴露于人体血液时，会与多种血浆成分相互作用，形成生物分子冠。这种冠层调节下游的生物学反应，包括与人免疫细胞的识别和结合。人们投入了大量的研究精力来设计能够表现出对各种蛋白质低亲和力（低污染材料）和与人免疫细胞低结合能力（隐形材料）的材料。生物纳米研究中一个共同的隐含假设是，低污染的纳米工程颗粒也将具有隐形特性。在此，我们研究了颗粒的低污染特性与其在全血中隐形特性之间的联系。合成了高污染的介孔二氧化硅（MS）颗粒和低污染的两性离子聚（2-甲基丙烯酰氧基乙基磷酸胆碱）（PMPC）颗粒，并在预涂血清白蛋白、免疫球蛋白 G 或补体蛋白 C1q 前后评估了它们与血液成分的相互作用。我们对生物分子冠进行了深入的蛋白质组学表征，既鉴定了特定的蛋白质，又测量了它们的相对丰度。这与全血结合测定的观察结果进行了比较，该测定确定了每个颗粒系统与哪种细胞类型结合。与基于 MS 的颗粒相比，基于 PMPC 的颗粒与细胞和血清蛋白的结合减少。此外，生物分子冠层中特定蛋白质的富集被发现与与特定细胞类型的结合相关。这项研究表明，材料的低污染特性如何指示其对免疫细胞结合的隐形特性。
