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

• Published in: ACS nano Vol. 16; no. 1; pp. 1036 - 1050
• Main Authors: Chen, Xu, He, Xiaoyun, Gao, Ruxin, Lan, Xinyue, Zhu, Longjiao, Chen, Keren, Hu, Yanzhou, Huang, Kunlun, Xu, Wentao
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.01.2022
• Subjects: Adipose Tissue, Brown; Adipose Tissue, White; Drug Delivery Systems; Energy Metabolism; Humans; Obesity - drug therapy; Thermogenesis; binary-drug; aptamer; rolling circle amplification; G-quadruplex; uncoupling protein-1; targeted delivery; obesity
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.1c08690

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 via 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. In vivo 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.