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

• Published in: Advanced materials (Weinheim) 2021-07, Vol.33 (29), p.e2008457-n/a
• Main Authors: Wang, Yang, Benson, Erik, Fördős, Ferenc, Lolaico, Marco, Baars, Igor, Fang, Trixy, Teixeira, Ana I., Högberg, Björn
• Format: Article
• Language: English
• Subjects: Biocompatibility; Cell Line, Tumor; cell spheroid tissue model penetration; Cell Survival - drug effects; cell uptake; Design; DNA - chemistry; DNA - metabolism; DNA origami design; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; drug delivery; Formability; Humans; Materials science; Medicin och hälsovetenskap; Nucleic Acid Conformation; Penetration; Receptors; Rods; Spheroids, Cellular - cytology; Spheroids, Cellular - metabolism; Structural design; structure flexibility; Toxicity
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202008457

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. To probe the potential for DNA‐origami‐based delivery devices, the effect of the folding arrangement of the DNA, on passive uptake and penetration, is studied. Despite almost identical composition and shape of the structures, wireframe‐style origami penetrates deeper in tumor models than classical origami and this is likely an effect due to differences in scavenger receptor mediated uptake.