Time Evolution of Nanoparticle–Protein Corona in Human Plasma: Relevance for Targeted Drug Delivery

When nanoparticles (NPs) enter a
biological fluid (e.g., human
plasma (HP)), proteins and other biomolecules adsorb on the surface
leading to formation of a rich protein shell, referred to as “protein
corona”. This corona is dynamic in nature and its composition
varies over time due to continuous protein association and dissociation
events. Understanding the time evolution of the protein corona on
the time-scales of a particle’s lifetime in blood is fundamental
to predict its fate in vivo. In this study, we used lipid NPs, the
cationic lipid 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl] (DC-Chol) and
the zwitterionic lipid dioleoylphosphatidylethanolamine (DOPE), that
are among the most promising nanocarriers both in vitro and in vivo.
Here, we investigated the time evolution of DC-Chol–DOPE NPs
upon exposure to HP. On time scales between 1 and 60 minutes, nanoliquid
tandem mass spectrometry revealed that the protein corona of DC-Chol–DOPE
NPs is mainly constituted of apolipoproteins (Apo A-I, Apo C–II,
Apo D, and Apo E are the most enriched). Since the total apolipoprotein
content is relevant, we exploited the protein corona to target PC3
prostate carcinoma cell line that expresses high levels of scavenger
receptor class B type 1 receptor, which mediates the bidirectional
lipid transfer between low-density lipoproteins, high-density lipoproteins,
and cells. Combining laser scanning confocal microscopy experiments
with flow cytometry we demonstrated that DC-Chol–DOPE/HP complexes
enter PC3 cells by a receptor-mediated endocytosis mechanism.