One‐Pot Controllable Assembly of a Baicalin‐Condensed Aptamer Nanodrug for Synergistic Anti‐Obesity

Abstract The rapid, simple and low‐cost preparation of DNA micro‐nano‐architectures remain challenging in biosensing and therapy. Polymerase chain reaction (PCR)‐driven DNA micro‐nano‐flowers are used to construct a nanosized baicalin‐compressed‐aptamer‐nanodrug (bcaND) via one‐pot assembly for targeted and synergistic anti‐obesity. In the design, the tailored Adipo‐8 (tAdi‐8) overhang in the PCR amplicon displays anti‐obesity targeting activity, while the baicalin loaded in the bcaND by embedding the amplicon plays a three‐fold role as a lipid‐lowering factor, bcaND size compressor, and uncoupling protein‐1 ( UCP1 )‐raised thermogenic activator. The ingenious bcaND represents an advanced multifunctional nanomaterial capable of adjusting the morphology at an optimal 400/1 molar ratio of Mg 2+ to phosphate groups, compressing the size from 2.699 µm to 214.76 nm using 1 mg/mL baicalin at a temperature of 70 °C, an effective payload with amplicons of up to 98.94%, and a maximum baicalin load of 86.21 g/g DNA. Responsive release in acidic conditions (pH 5.0) occurs within 72 h, accelerating thermogenesis via UCP1 up‐regulation by 2.5‐fold in 3T3‐L1‐preadipocytes and 13.7‐fold in the white‐adipose‐tissue (WAT) of mice, targeting adipocytes and visceral white adipose tissue. It plays an efficient synergistic role in obesity therapy in vitro and in vivo, providing a new direction for DNA self‐assembly nanotechnology.