DNA nanostructures are well-established vectors for packaging diversified payloads for targeted cellular delivery. Here, DNA origami rectangular sheets were combined with Herpes Simplex Virus 1 (HSV1) capsids to demonstrate surface coverage of the particle via electrostatic interactions. The optimized origami:HSV1 molar ratios led to characteristic packaging geometries ranging from dispersed HSV1 pockets to agglomerated HSV1 sleeves. Pockets were disguised from cells in HeLa and B16F10 cells and were 44.2% less infective than naked HSV1 particles. However, the pockets were 117% more infective than naked HSV1 particles when the origami sheets were coated with folic acid. We observed infectivity from naked origami, but they are 99.1% less infective with respect to HSV1 and 99.6% less infective with respect to the pocket complexes. This work suggests that DNA origami can selectively modulate virus infectivity.

The interest in using therapeutic nanoparticles to bind with harmful molecules or pathogens and subsequently neutralize their bioactivity has grown tremendously. Among various nanomedicine platforms, cell membrane-coated nanoparticles, namely, cellular nanosponges, stand out for their broad-spectrum neutralization capability challenging to achieve in traditional countermeasure technologies. Such ability is attributable to their cellular function-based rather than target structure-based working principle. Integrating cellular nanosponges with various synthetic substrates further makes their applications exceptionally versatile and adaptive. This review discusses the latest cellular nanosponge technology focusing on how the structure-function relationship in different designs has led to versatile and potent medical countermeasures. Four design strategies are discussed, including harnessing native cell membrane functions for biological neutralization, functionalizing cell membrane coatings to enhance neutralization capabilities, combining cell membranes and functional cores for multimodal neutralization, and integrating cellular nanosponges with hydrogels for localized applications. Examples in each design strategy are selected, and the discussion is to highlight their structure-function relationships in complex disease settings. The review may inspire additional design strategies for cellular nanosponges and fulfill even broader medical applications.