4.8 Article

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

Journal

SMALL
Volume 19, Issue 6, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202205933

Keywords

aptamers; baicalin; controllable assembly; nanodrugs; obesity therapies

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The rapid, simple and low-cost preparation of DNA micro-nano-architectures remains a challenge in biosensing and therapy. To address this, a nanosized baicalin-compressed-aptamer-nanodrug (bcaND) was constructed using polymerase chain reaction (PCR)-driven DNA micro-nano-flowers. The bcaND showed targeted and synergistic anti-obesity effects by combining the anti-obesity activity of tailored Adipo-8 (tAdi-8) overhang in the PCR amplicon and the lipid-lowering, size compression, and thermogenic activation properties of baicalin.
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 Mg2+ to phosphate groups, compressing the size from 2.699 mu m to 214.76 nm using 1 mg/mL baicalin at a temperature of 70 degrees 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.

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