Orientation of surface-immobilized DNA tetrahedron nanostructures dictates cell–material interaction

Abstract

The versatile chemistry of DNA nanostructures enables the development of spatially controlled hybrid nanomaterials for applications in biosensing and nanomedicine. Despite extensive progress, precise control over their cellular interactions remains challenging. Here, we demonstrate a strategy that harnesses DNA NS with prescribed orientations on various materials to modulate the cellular interaction. Using spherical polystyrene nanoparticles, we demonstrate that DNA tetrahedron nanostructures (TDNs) with corner-protruding geometry enhance uptake efficiency by up to 8.4-fold. Mechanistic studies reveal that TDN orientation modulates configuration entropy at the cell–material interface, with vertex-aligned TDNs reducing entropy penalties to optimize receptor engagement. Moreover, tailoring TDN orientations serves as a general strategy to control cell–material interactions, as demonstrated with graphene oxides of varying sizes, enhancing their ability for membrane disruption and efficient cytoplasmic delivery. Overall, our findings establish TDN orientation as a design principle for tuning cell–material interactions, offering new opportunities for DNA-functionalized nanomaterials in nanomedicine, diagnostics, and biointerface engineering.