Dual-Targeted Glucose-Dependent Insulinotropic Polypeptide-Loaded Photothermal Nanoparticles to Prevent Obesity via Lipolysis and Browning of White Adipose Tissue

Abstract

Obesity, a manifestation of energy imbalance, has become a global health pandemic. However, current pharmacological treatments, which target the central nervous system to suppress appetite and the gastrointestinal tract to inhibit nutrient absorption, have inevitably led to adverse effects, for example, depression or muscle loss. And here is limited research and development on drugs that promote energy expenditure. This study aims to construct dual-targeted glucose-dependent insulinotropic polypeptide (GIP)-loaded photothermal nanoparticles (GIP/ICG@P/R8 NPs), to target white adipose tissue (WAT) and induce energy expenditure through adipose tissue remodeling. The results reveal that GIP/ICG@P/R8 NPs effectively promoted energy expenditure by inducing browning, lipolysis, and apoptosis of WAT in vitro and in vivo, outperforming single GIP or photothermal therapy. Furthermore, treatment with GIP/ICG@P/R8 NPs effectively improves systemic metabolic profiles, including a 9.23% reduction in body weight after 14 days, enhanced insulin sensitivity, and amelioration of fatty liver. Beyond that, targeted drug delivery has demonstrated favorable safety profiles, as evidenced by the absence of significant morphological or pathological changes in major organs and muscle tissues following administration. In summary, this dual-targeted NPs platform represents a promising strategy for combating obesity and related metabolic diseases.