Abstract
It is hypothesized that plasma proteins bind nanoparticles in vivo as they do in vitro, forming a protein corona. The resulting decorated nanoparticle surface could potentially alter nanoparticle pharmacokinetics, efficacy, and toxicity in vivo. A subset of the in vitro corona are high-density lipoproteins (HDLs). Since HDLs vary in patients based on diet, weight, and genetics, it is crucial to determine the affinity of HDLs for nanoparticles to generate a predictive model, which would provide information on the extent of HDL decoration on nanoparticles in the blood. Experiments that determined equilibrium affinities of HDLs for nanoparticles utilized isolated HDLs or HDL structural protein components such as ApoA-I. Thus, the effects of whole plasma on HDL-nanoparticle equilibrium binding are unclear. It is possible that competition from other plasma proteins for the nanoparticle surface could drastically change the affinity of HDLs for nanoparticles both in vitro and in vivo. Here, we determined effective equilibrium binding constants of Kdeff = 3.1 ± 0.7 μM, 1.2 ± 0.4 μM, and 2.0 ± 0.4 μM for polystyrene (PS), PS-COOH, and PS-NH2 nanospheres for ApoA-I, the main structural component of HDLs in whole mouse plasma. In comparison, binding constants were Kd = 400 nM, 900 nM, and 25 nM for PS, PS-COOH, and PS-NH2 nanospheres and HDLs isolated from mouse plasma. We utilized a binding model that is characterized by a nanoparticle with multiple identical and independent binding sites for HDLs. Our data show that HDL binding to nanoparticles could play a significant role in nanoparticle behavior in the vasculature of mammals.
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Acknowledgements
We thank Dr. Eric Tague for mass spectrometry. We also thank Dr. Edward Wright and Liang Fang for their support with the isothermal titration calorimetry and gel filtration chromatography column, respectively.
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This work was supported by the National Institute of General Medical Sciences R15GM116037.
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Anozie, U.C., Quigley, K.J., Prescott, A. et al. Equilibrium binding of isolated and in-plasma high-density lipoproteins (HDLs) to polystyrene nanoparticles. J Nanopart Res 22, 223 (2020). https://doi.org/10.1007/s11051-020-04953-0
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DOI: https://doi.org/10.1007/s11051-020-04953-0