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

Hugo J Rodríguez-Franco; Jorieke Weiden; Maartje M C Bastings

doi:10.1021/acspolymersau.3c00009

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

ACS Polym Au. 2023 Jun 7;3(4):344-353. doi: 10.1021/acspolymersau.3c00009. eCollection 2023 Aug 9.

Authors

Hugo J Rodríguez-Franco¹, Jorieke Weiden¹, Maartje M C Bastings¹

Affiliation

¹ Programmable Biomaterials Laboratory, Institute of Materials, Interfaculty Bioengineering Institute, School of Engineering, Ecole Polytechnique Fédérale Lausanne, Lausanne 1015, Switzerland.

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.