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

Abstract

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.

Modulating the DNA/Lipid Interface through Multivalent Hydrophobicity

“…Our current study included a small series of readily available molecules. With the development of DNA modification, systematic studies comparing other hydrophobic moieties, for example poly(propylene oxide) (PPO) or porphyrin, and alkyne chains should be considered. This would build toward a framework for designing and predicting DNA biomaterial interactions with lipid membranes, highlighting their versatility and reliability as molecular tools for controlling modified DNA/lipid interactions.…”

Balancing the Nanoscale Organization in Multivalent Materials for Functional Inhibition of the Programmed Death-1 Immune Checkpoint

“…In contrast to other available nanoparticles, DNA origami offers perfect control over size, shape, and surface properties guaranteeing uniform particle design. In addition to their inherent biocompatibility, the modulatory properties of nucleic acid-based systems allow the positioning of individual ligand with nanometer precision. − Benefiting from efforts on structural stabilization and surface characterization, the stability of DNA origami in biological environments as well as interactions with the biointerface are now well understood. − Together, these features make DNA origami a platform for controlled ligand presentation for receptor binding susceptible to nanoscale ligand presentation.…”

“… 29 − 34 Benefiting from efforts on structural stabilization and surface characterization, the stability of DNA origami in biological environments as well as interactions with the biointerface are now well understood. 35 − 37 Together, these features make DNA origami a platform for controlled ligand presentation for receptor binding susceptible to nanoscale ligand presentation.…”