Engineering DNA Condensate Droplets as a Versatile Nanovector

Biomolecular condensates play important roles in molecular transport within living organisms and have emerged as a promising delivery vehicle for biopharmaceutical applications. Here, we report on the engineering of DNA condensates (DNA droplets) as versatile nanovectors by utilizing their hierarchical structure. Hierarchically structured DNA droplets offer multiple drug loading sites through the utilization of covalent modifications on the primary structure (phosphate backbone), noncovalent interactions on the secondary structure (grooves), or physical retention on higher-order structure (pores). We found that DNA droplets are capable of loading small molecules and amino-based cargo through noncovalent or covalent interactions. The spatial position of different cargos loaded onto DNA droplets can be precisely controlled. Additionally, DNA droplets can effectively scavenge reactive oxygen species. This study demonstrates that DNA droplets can provide multiple drug loading sites and precisely control the positions of different drugs, making DNA droplets a promising functional nanovector for drug delivery.