Protein Corona of Nanoparticles: Distinct Proteins Regulate the Cellular Uptake

Understanding nanoparticle–protein
interactions is a crucial
issue in the development of targeted nanomaterial delivery. Besides
unraveling the composition of the nanoparticle’s protein coronas,
distinct proteins thereof could control nanoparticle uptake into specific
cell types. Here we differentially analyzed the protein corona composition
on four polymeric differently functionalized nanoparticles by label-free
quantitative mass spectrometry. Next, we correlated the relative abundance
of identified proteins in the corona with enhanced or decreased cellular
uptake of nanoparticles into human cancer and bone marrow stem cells
to identify key candidates. Finally, we verified these candidate proteins
by artificially decorating nanoparticles with individual proteins
showing that nanoparticles precoated with the apolipoproteins ApoA4
or ApoC3 significantly decreased the cellular uptake, whereas precoating
with ApoH increased the cellular uptake.