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

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

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,...

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Bibliographic Details
Published in:ACS applied materials & interfaces Vol. 13; no. 39; pp. 46375 - 46390
Main Authors: Smolková, Barbora, MacCulloch, Tara, Rockwood, Tyler F, Liu, Minghui, Henry, Skylar J. W, Frtús, Adam, Uzhytchak, Mariia, Lunova, Mariia, Hof, Martin, Jurkiewicz, Piotr, Dejneka, Alexandr, Stephanopoulos, Nicholas, Lunov, Oleg
Format: Journal Article
Language:English
Published: United States American Chemical Society 06-10-2021
Subjects:
Adsorption
Antimicrobial Cationic Peptides - chemistry
Antimicrobial Cationic Peptides - metabolism
Biological and Medical Applications of Materials and Interfaces
Cell Line, Tumor
DNA - chemistry
DNA - metabolism
Endosomes - metabolism
Humans
Lysosomes - metabolism
Nanostructures - chemistry
Nucleic Acid Conformation
Protein Corona - chemistry
Protein Corona - metabolism
nanotechnology
DNA nanotechnology
endolysosomal escape
bionano interactions
protein corona
cellular uptake
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Summary: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.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.1c14401