Protein Corona Inhibits Endosomal Escape of Functionalized DNA Nanostructures in Living Cells

• DOI: 10.1021/acsami.1c14401
• Publication Date: 2021-09-27T22:06:35Z
• Authors: Barbora Smolková; Tara MacCulloch; Tyler F. Rockwood; Minghui Liu; Skylar J. W. Henry; Adam Frtús; Mariia Uzhytchak; Mariia Lunova; Martin Hof; Piotr Jurkiewicz; Alexandr Dejneka; Nicholas Stephano...; Oleg Lunov
• Keywords: biomedical applications; 0301 basic medicine; endolysosomal escape; Biochemistry; therapeutic agents; biological response; dn biological activity; DNA nanotechnology; protein corona determines; functionalized dns; nanotechnology; programmable manner; study offers; cell size; increasingly used; biological liquids; well established; linearly dependent; Medicine; Protein Corona; functionalized dna nanostructures; living cells; Biotechnology; Chemical Sciences not elsewhere classified; analysis indicates; Biophysics; 612; Endosomes; Inorganic Chemistry; important basis; 03 medical and health sciences; protein corona; Cell Line, Tumor; Genetics; various biomedical applications; Humans; turn modulates; Pharmacology; future optimization; limited studies; endosome escape peptide; nanomaterials become covered; cellular uptake; Cell Biology; DNA; Nanostructures; Nucleic Acid Conformation; bionano interactions; Adsorption; Lysosomes; Developmental Biology; Antimicrobial Cationic Peptides

DNA nanostructures (DNs) can be designed in a controlled and programmable manner, and these structures are increasingly used in a variety of biomedical applications, such as the delivery of therapeutic agents. When exposed to biological liquids, most nanomaterials become covered by a protein corona, which in turn modulates their cellular uptake and the biological response they elicit. However, the interplay between living cells and designed DNs are still not well established. Namely, there are very limited studies that assess protein corona impact on DN biological activity. Here, we analyzed the uptake of functionalized DNs in three distinct hepatic cell lines. Our analysis indicates that cellular uptake is linearly dependent on the cell size. Further, we show that the protein corona determines the endolysosomal vesicle escape efficiency of DNs coated with an endosome escape peptide. Our study offers an important basis for future optimization of DNs as delivery systems for various biomedical applications.