Nanoparticles have been attracting tremendous attention for drug delivery and bioimaging up to date. However, the nanoparticles for live cell monitoring and tracking of cytoplasmic processes still remain limited due to inefficient delivery methods, altered state or function of cells during the delivery process and the requirement of surface-functionalized nanoparticles for specific labeling of subcellular structures. In addition, current understanding and connection between the physicochemical characteristics of a nanomaterial and its interactions with a physiological system are unclear. Here, we investigate the role of surface chemistry in mediating serum protein adsorption to the nanoparticles and their cellular uptake. To suppress protein adsorption or nonspecific bindings, researchers often functionalize the nanoparticle surface with the antifouling polyethylene glycol (PEG). The relative density of the serum proteins depends on the nanoparticle size and the PEG grafting density, and variations in serum protein adsorption is further correlated with the uptake mechanism and efficiency of nanoparticle. Thus, PEG density and nanoparticle size together determine the mechanism and efficiency of cellular binding and uptake, probably by controlling either the identity or accessibility of adsorbed serum proteins. Although PEG can facilitate the reduction of nonspecific binding to cells, this process is not as simple as just putting PEG on the surface, since the chain length of the PEG has to be less than that of the ligand linker in order to not interfere with the binding of the targeting moiety (e.g. peptide) to its target receptor. Our study provides controllable manner of nanoparticle uptake by changing nanoparticle size and surface chemistry, and ultimately establishes principles for the rational design of clinically useful nanoparticle for translational uses of nanomedicine.

Assessing the effect of surface chemistry on targeted delivery and cellular uptake of silica nanoparticle

2019 Fall National Meeting

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