Protein Corona of Nanoparticles: Distinct Proteins Regulate the Cellular Uptake

TLDR

Nanoparticle–protein interactions are critical for targeted delivery, and the composition of the protein corona may dictate cellular uptake into specific cell types. The study aimed to identify proteins that regulate nanoparticle uptake by correlating corona protein abundance with uptake in human cancer and bone marrow stem cells. Four polymeric nanoparticles with distinct surface chemistries were analyzed by label‑free quantitative mass spectrometry to determine their protein corona composition, and the relative abundance of each protein was correlated with cellular uptake. Decorating nanoparticles with ApoA4 or ApoC3 reduced uptake, while ApoH increased uptake, confirming these proteins as key regulators of cellular internalization.

Abstract

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.