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DNA Origami Penetration in Cell Spheroid Tissue Models is Enhanced by Wireframe Design.

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Title: DNA Origami Penetration in Cell Spheroid Tissue Models is Enhanced by Wireframe Design.
Authors: Wang Y; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Benson E; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Fördős F; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Lolaico M; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Baars I; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Fang T; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Teixeira AI; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden., Högberg B; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SE-17177, Sweden.
Source: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2021 Jul; Vol. 33 (29), pp. e2008457. Date of Electronic Publication: 2021 Jun 06.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 9885358 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4095 (Electronic) Linking ISSN: 09359648 NLM ISO Abbreviation: Adv Mater Subsets: MEDLINE
Imprint Name(s): Publication: Sept. 3, 1997- : Weinheim : Wiley-VCH
Original Publication: Deerfield Beach, FL : VCH Publishers, 1989-
MeSH Terms: DNA*, Nanotechnology ; Nucleic Acid Conformation
Abstract: As DNA origami applications in biomedicine are expanding, more knowledge is needed to assess these structures' interaction with biological systems. Here, uptake and penetration in cell and cell spheroid tissue models (CSTMs) are studied to elucidate whether differences in internal structure can be a factor in the efficacy of DNA-origami-based delivery. Two structures bearing largely similar features in terms of both geometry and molecular weight, but with different internal designs-being either compact, lattice-based origami or following an open, wireframe design-are designed. In CSTMs, wireframe rods are able to penetrate deeper than close-packed rods. Moreover, doxorubicin-loaded wireframe rods show a higher cytotoxicity in CSTMs. These results can be explained by differences in structural mechanics, local deformability, local material density, and accessibility to cell receptors between these two DNA origami design paradigms. In particular, it is suggested that the main reason for the difference in penetration dynamic arises from differences in interaction with scavenger receptors where lattice-based structures appear to be internalized to a higher degree than polygonal structures of the same size and shape. It is thus argued that the choice of structural design method constitutes a crucial parameter for the application of DNA origami in drug delivery.
(© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)
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Grant Information: 724872 International ERC_ European Research Council
Contributed Indexing: Keywords: DNA origami design; cell spheroid tissue model penetration; cell uptake; drug delivery; structure flexibility
Substance Nomenclature: 9007-49-2 (DNA)
Entry Date(s): Date Created: 20210607 Date Completed: 20211216 Latest Revision: 20230918
Update Code: 20230918
PubMed Central ID: PMC7613750
DOI: 10.1002/adma.202008457
PMID: 34096116
Database: MEDLINE
Description
ISSN:1521-4095
DOI:10.1002/adma.202008457