Fusion Aptamer-Lactoferrin Delivery System for Targeted Delivery to Adipose Tissue and the Amelioration of Obesity

Targeted delivery of natural products to the distal regions of adipose tissue for comprehensive metabolic regulation remains a significant challenge. In this study, we developed molecular self-assembling nanocarriers using a bottom-up self-assembly strategy incorporating fusion aptamers. First, we designed a lactoferrin-adipocyte fusion aptamer capable of simultaneously binding lactoferrin and targeting adipocytes. Subsequently, an adipose tissue-targeted delivery system was constructed through rolling circle amplification and the self-assembly of lactoferrin and aptamer binding. This system effectively facilitated the loading, transport, and targeted release of allicin, significantly enhancing its bioavailability. The incorporation of lactoferrin notably reduced the particle size of multivalent aptamer nanocarriers while improving their tissue permeability in 3D adipocyte spheroids. By binding to and activating SIRT1, allicin delivered via this system promotes the beiging of adipocytes and enhances overall lipid metabolism, demonstrating superior antiobesity effects. In summary, the lactoferrin-functionalized nucleic acid-allicin delivery system represents a promising tool for antiobesity applications.