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

Area of Science:

• Biotechnology
• Nanomedicine
• Obesity Therapeutics

Background:

• Targeted delivery of phytochemicals for obesity therapy is challenging.
• Allicin, a phytochemical, can induce adipose tissue browning and promote energy expenditure.
• Developing effective drug delivery systems for obesity treatment is crucial.

Purpose of the Study:

• To develop a synergistic, adipocyte-targeted binary-drug delivery system for obesity therapy.
• To utilize a functionalized adipo-8 aptamer loaded with allicin for enhanced delivery to white adipose tissue.
• To investigate the efficacy of the DNA-nanoflower-allicin (NFA) framework in promoting adipocyte browning and energy expenditure.

Main Methods:

• Assembly of a functionalized adipo-8 aptamer loaded with allicin using isothermal rolling-circle techniques.
• Characterization of the DNA-nanoflower-allicin (NFA) framework, including size reduction and cellular uptake efficiency.
• Confocal microscopy for intracellular distribution and lysosomal escape assessment.
• In vivo studies in animal models to evaluate NFA's effect on adipocyte browning and energy expenditure.

Main Results:

• The NFA system efficiently encapsulated, transported, and released allicin into white adipose tissue.
• NFA demonstrated increased cellular uptake efficiency (up to 118.7%) and reduced nanoparticle size (from 770 to 380 nm).
• In vivo administration of NFA promoted adipocyte browning and systemic energy expenditure with minimal side effects.
• The G-quadruplex in the mitochondrial uncoupling protein-1 promoter was identified as an allicin target for thermogenesis regulation.

Conclusions:

• The adipo-8 aptamer-allicin binary-drug delivery system (NFA) shows significant potential for obesity therapy.
• NFA facilitates targeted delivery of allicin to white adipose tissue, enhancing its therapeutic effects.
• This novel approach effectively promotes adipocyte browning and energy expenditure, offering a promising strategy to combat obesity.