Temperature-Responsive Nanoparticles Enable Specific Binding of Apolipoproteins from Human Plasma

Abstract

Apolipoproteins are an important class of proteins because they provide a so-called stealth effect to nanoparticles. The stealth effect on nanocarriers leads to a reduced unspecific uptake into immune cells and thereby to a prolonged blood circulation time. Herein, a novel strategy to bind apolipoproteins specifically on nanoparticles by adjusting the temperature during their incubation in human plasma is presented. This specific binding, in turn, allows a control of the stealth behavior of the nanoparticles. Nanoparticles with a well-defined poly(N-isopropylacrylamide) shell are prepared, displaying a reversible change of hydrophobicity at a temperature around 32 °C. It is shown by label-free quantitative liquid chromatography-mass spectrometry that the nanoparticles are largely enriched with apolipoprotein J (clusterin) at 25 °C while they are enriched with apolipoprotein A1 and apolipoprotein E at 37 °C. The temperature-dependent protein binding is found to significantly influence the uptake of the nanoparticles by RAW264.7 and HeLa cells. The findings imply that the functionalization of nanoparticles with temperature-responsive materials is a suitable method for imparting stealth properties to nanocarriers for drug-delivery.