Stabilizing Polymer Coatings Alter the Protein Corona of DNA Origami and Can Be Engineered to Bias the Cellular Uptake

With DNA-based nanomaterials being designed for applications
in
cellular environments, the need arises to accurately understand their
surface interactions toward biological targets. As for any material
exposed to protein-rich cell culture conditions, a protein corona
will establish around DNA nanoparticles, potentially altering the
a-priori designed particle function. Here, we first set out to identify
the protein corona around DNA origami nanomaterials, taking into account
the application of stabilizing block co-polymer coatings (oligolysine-1kPEG
or oligolysine-5kPEG) widely used to ensure particle integrity. By
implementing a label-free methodology, the distinct polymer coating
conditions show unique protein profiles, predominantly defined by
differences in the molecular weight and isoelectric point of the adsorbed
proteins. Interestingly, none of the applied coatings reduced the
diversity of the proteins detected within the specific coronae. We
then biased the protein corona through pre-incubation with selected
proteins and show significant changes in the cell uptake. Our study
contributes to a deeper understanding of the complex interplay between
DNA nanomaterials, proteins, and cells at the bio-interface.