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

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.

Automated summary

This study investigates the uptake and penetration of DNA origami structures in cell and cell spheroid tissue models to evaluate the efficacy of DNA origami-based delivery. The results show that wireframe rods can penetrate deeper and exhibit higher cytotoxicity in CSTMs compared to lattice-based rods. The choice of structural design method is suggested to be a crucial parameter for the application of DNA origami in drug delivery based on differences in structural mechanics and interaction with cell receptors.