The protein binding propensity of nanoparticles determines their in vivo toxicity and their fate to be opsonized and cleared by human defense systems. In this work, protein-binding mechanisms of pristine and functionalized multiwalled carbon nanotubes (f-MWNTs) were investigated by varying f-MWNTs' diameters, nanotube surface chemistry, and proteins using steady-state and time-resolved fluorescence, and circular dichroism (CD) spectroscopies. The f-MWNTs with a larger diameter (∼40 nm) generally exhibited stronger protein binding compared to those with a smaller diameter (∼10 nm), demonstrating that the curvature of nanoparticles plays a key role in determining the protein binding affinity. Negative charges or steric properties on f-MWNTs enhanced binding for some proteins but not others, indicating that the electrostatic and stereochemical nature of both nanotubes and proteins govern nanotube/protein binding. Protein fluorescence lifetime was not altered by the binding while the intensity was quenched indicating a static quenching through complex formation. The binding-induced conformational changes were further confirmed by CD studies.
Although nanoparticle/protein binding and the cytotoxicity of nanoparticles have been separately reported, there has been no study linking the nature of nanoparticle/protein clusters to cell uptake and the dynamic cellular responses. We report here that water-soluble iron oxide-based magnetic nanoparticles (MNPs) with different sizes and surface chemistry bind different serum proteins in terms of protein identity and quantity without changing the protein secondary structures. Carboxylated MNPs (and aminated one in smaller MNPs) resulted in higher cytotoxicity, and PEG coating reduced both cell uptake and the cytotoxicity. Smaller MNPs (especially the carboxylated one) bind more serum proteins, are much less taken up by cells as compared to larger particles, and yet elicit more dynamic cytotoxic responses. Besides the intrinsic effects of size and surface charge of the water-soluble MNPs, the cellular effects of MNPs/protein clusters were also attributed to the identity and quantity of the adsorbed proteins rather than the binding-induced new epitopes on the proteins.
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