Hierarchical Self-Assembly of Disulfide-Linked Single-Stranded DNA into Stimuli-Responsive Pods

Controlling the large-scale assembly of charged biopolymers is a fundamental challenge in materials chemistry. Here, we report a chemical strategy that uses disulfide-linked single-stranded DNA (ssDNA) dimers as unique building blocks to drive the hierarchical self-assembly of functional DNA microstructures. Formed from short, random-sequence oligomers, these dimers first organize into DNA-salt composite nanobead condensates, which then serve as scaffolds for the assembly of uniform, microrod-shaped DNA condensates called DNA-pod condensates. The key innovation of this work is the material’s unique, cooperative structural transition. Upon thermal stimulation (>60 °C), dsDNA-pod condensates undergo a rapid exfoliation into an expanded ssDNA network, a process driven by significant gains in configurational entropy and the relief of electrostatic repulsion. This establishes an accessible strategy for creating stimuli-responsive DNA materials through a chemistry-driven, sequence-independent pathway. We further demonstrate that these materials act as robust host matrices for encapsulating guest molecules like doxorubicin.