Nanoparticle Size and Surface Chemistry Determine Serum Protein Adsorption and Macrophage Uptake

TLDR

Delivery and toxicity are critical issues in nanomedicine, and the physicochemical properties of nanomaterials—often called their synthetic identity—do not fully predict their interactions in vivo, as serum protein adsorption and phagocyte interactions alter their size, aggregation, and interfacial composition, thereby creating a distinct biological identity that affects delivery, redistribution, and toxicity. The study investigates how nanoparticle size and surface chemistry affect serum protein adsorption and subsequent macrophage uptake. The authors analyze gold nanoparticles of different sizes and PEG grafting densities to assess protein adsorption patterns and uptake mechanisms. Over 70 serum proteins adsorb heterogeneously to gold nanoparticles, with protein density depending on size and PEG density, and these variations correlate with differences in macrophage uptake efficiency, establishing principles for rational nanomaterial design.

Abstract

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.