Au clusterzymes encapsulated in nanogel activated by alternating magnetic field to promote white fat browning and combat obesity.

Obesity, a major global public-health challenge, is a well-established risk factor for numerous metabolic disorders. In this study, we developed a novel nanosystem based on Au clusterzymes (AuCZy) encapsulated in chitosan (CS) and functionalized with an adipose homing peptide (AHP), referred to as AHP-AuCZy@CS nanogel. Specifically, an alternating magnetic field (AMF) was applied to modulate its enzyme-mimicking activity. It was found that AMF stimulation significantly enhanced SOD-like and CAT-like activities, endowing AHP-AuCZy@CS nanogels with superior reactive oxygen species (ROS) scavenging capacity. Furthermore, in vivo experiments demonstrated the efficient targeting of AHP-AuCZy@CS nanogels to white adipose tissue (WAT). After a 45-day treatment regimen (once every three days) with AHP-AuCZy@CS nanogels combined with AMF, obese mice exhibited an 18% reduction in body weight compared to the control group. This combination treatment also suppressed WAT expansion, improved glucose tolerance and insulin sensitivity, and ameliorated lipid metabolic disorders. Mechanistic investigations revealed that AMF-enhanced ROS scavenging by AHP-AuCZy@CS nanogels activated the AMPK signaling pathway, promoting white fat browning and thermogenesis. This work demonstrates the compelling therapeutic potential of clusterzymes combined with AMF for the treatment of obesity and associated metabolic diseases.