Aptamer-Functionalized Binary-Drug Delivery System for Synergetic Obesity Therapy.

The targeted delivery of phytochemicals that promote energy expenditure for obesity therapy remains a challenge. This study assembled a functionalized adipo-8 aptamer loaded with allicin using isothermal rolling-circle techniques to form a synergistic adipocyte-targeted binary-drug delivery system for treating obesity. The functionalized adipo-8 aptamer efficiently protected allicin from adsorption, showing significant potential to encapsulate, transport, and release molecular cargos into white adipose tissue. Introducing the negatively charged allicin, a phytochemical able to induce adipose tissue browning, reduced the diameters of DNA-nanoflower from 770 to 380 nm and increased cellular uptake efficiency up to 118.7%. The intracellular distribution observed <i>via</i> confocal microscopy confirmed the successful receptor recognition mediated by aptamers in the DNA-nanoflower-allicin (NFA) framework as well as its excellent stability to escape from lysosomes. <i>In vivo</i> results demonstrated that subcutaneous administration of NFA effectively promoted adipocyte browning and systematic energy expenditure with minimal side effects. Furthermore, the G-quadruplex in the mitochondrial uncoupling protein-1 promoter was found to be an interactive allicin target for regulating thermogenesis to combat obesity.