Comprehensive Evaluation of Human and Murine Protein Coronae Formed on Choline Carboxylic Acid Ionic Liquid-Modified PLGA Nanoparticles

Despite decades of research, the successful clinical
translation
of intravenously administered nanomedicines is underwhelming. One
significant barrier to progress is the opsonization and rapid clearance
from the bloodstream due to protein corona formation as an innate
immune response. Biocompatible nanoparticle coatings that act as a
barrier between the nanomaterial and the physiological environment
are being continuously explored to elevate delivery success. However,
the formation and composition of protein coronae, especially across
species, are still poorly understood, which hinders the progress of
translation from preclinical animal models to human applications.
Here, we use quantitative protein assays, LC-MS proteomics, and machine
learning to catalog the protein coronae from human and mouse serum
formed on poly(lactic-co-glygolic) acid (PLGA) nanoparticles and explore
the impact of a large library of coatings comprised of cholinium fatty
acid–based ionic liquids (ILs) from 4- to 10-carbon chains
with varying degrees of unsaturation. We discover that the species
matters, with vast changes in the coronae being observed, depending
on the source of the serum sample. Additionally, even very small changes
in the ionic liquid anion structure result in the formation of diverse
hard coronae. We identify several ILs that show enriched dysopsonins
and depleted opsonins relative to serum that are promising candidates
for future development as therapeutics or in biosensing.