Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada M5S 3G9.
J Am Chem Soc. 2012 Feb 1;134(4):2139-47. doi: 10.1021/ja2084338. Epub 2012 Jan 23.
Delivery and toxicity are critical issues facing nanomedicine research. Currently, there is limited understanding and connection between the physicochemical properties of a nanomaterial and its interactions with a physiological system. As a result, it remains unclear how to optimally synthesize and chemically modify nanomaterials for in vivo applications. It has been suggested that the physicochemical properties of a nanomaterial after synthesis, known as its "synthetic identity", are not what a cell encounters in vivo. Adsorption of blood components and interactions with phagocytes can modify the size, aggregation state, and interfacial composition of a nanomaterial, giving it a distinct "biological identity". Here, we investigate the role of size and surface chemistry in mediating serum protein adsorption to gold nanoparticles and their subsequent uptake by macrophages. Using label-free liquid chromatography tandem mass spectrometry, we find that over 70 different serum proteins are heterogeneously adsorbed to the surface of gold nanoparticles. The relative density of each of these adsorbed proteins depends on nanoparticle size and poly(ethylene glycol) grafting density. Variations in serum protein adsorption correlate with differences in the mechanism and efficiency of nanoparticle uptake by a macrophage cell line. Macrophages contribute to the poor efficiency of nanomaterial delivery into diseased tissues, redistribution of nanomaterials within the body, and potential toxicity. This study establishes principles for the rational design of clinically useful nanomaterials.
递送和毒性是纳米医学研究面临的关键问题。目前，对于纳米材料的物理化学性质与其与生理系统的相互作用之间的理解和联系十分有限。因此，仍不清楚如何优化纳米材料的合成和化学修饰以用于体内应用。有人认为，纳米材料合成后的物理化学性质，即其“合成特性”，与细胞在体内遇到的情况并不相同。血液成分的吸附和与吞噬细胞的相互作用可以改变纳米材料的大小、聚集状态和界面组成，赋予其独特的“生物学特性”。在这里，我们研究了大小和表面化学在介导金纳米颗粒表面的血清蛋白吸附及其随后被巨噬细胞摄取中的作用。使用无标记液相色谱串联质谱法，我们发现超过 70 种不同的血清蛋白不均匀地吸附在金纳米颗粒的表面。这些吸附蛋白的相对密度取决于纳米颗粒的大小和聚乙二醇接枝密度。血清蛋白吸附的变化与巨噬细胞系摄取纳米颗粒的机制和效率的差异相关。巨噬细胞导致纳米材料在疾病组织中的递送效率低下、纳米材料在体内的重新分布以及潜在毒性。这项研究为合理设计临床有用的纳米材料奠定了基础。
