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

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 Stephanopoulos, Oleg Lunov

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)46375-46390
Number of pages16
JournalACS Applied Materials and Interfaces
Issue number39
StatePublished - Oct 6 2021


  • DNA nanotechnology
  • bionano interactions
  • cellular uptake
  • endolysosomal escape
  • nanotechnology
  • protein corona

ASJC Scopus subject areas

  • General Materials Science


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