Multifunctional DNA nanoflower recruits neural stem cells via ROS-responsive extracellular drug release to promote...

Progressive neuronal injury and death represent a shared challenge across nearly all forms of neurodegenerative diseases (NDs). A simple, safe, and inexpensive strategy that actively promotes neurogenesis is urgently needed. DNA nanoflowers (DNFs) are a new class of programmable DNA nanomaterials. Here we report a drug-loaded DNF (DAGC) that encodes both Apt 19S and G-rich sequences and carries chrysin. In vitro, DAGC recruits neural stem cells and drives their differentiation into neurons. In vivo, 300 nm DAGC restores cognitive function in model mice by boosting neurogenesis, reducing blood brain barrier leakage, and lowering Aβ accumulation; transcriptomic analysis confirms these effects. The G-rich module elevates chrysin loading and, under high ROS, undergoes Apurinic/Apyrimidinic (AP) site cleavage to release both Apt 19S and chrysin. Thus, the same nanostructure serves simultaneously as a controlled-release vehicle and a therapeutic agent, offering a promising route for treating NDs.