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

## TL;DR

Researchers developed a new nanoparticle treatment that targets fat tissue to reduce obesity and improve metabolism without harmful side effects.

## Contribution

A dual-targeted nanoparticle platform that promotes energy expenditure via lipolysis and browning of white adipose tissue.

## Key findings

- GIP/ICG@P/R8 NPs reduced body weight by 9.23% in 14 days and improved insulin sensitivity.
- The treatment induced browning, lipolysis, and apoptosis of white adipose tissue in vitro and in vivo.
- No significant adverse effects were observed in major organs or muscle tissues.

## 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.

Current weight‐loss medications inevitably cause adverse effects such as depression or muscle loss. The developed GIP/ICG@P/R8 NPs specifically promoted energy expenditure by inducing browning, lipolysis and apoptosis of WAT in vitro and in vivo. The results showed a 9.23% weight reduction after 14 days, enhanced insulin sensitivity, improved fatty liver condition, excellent safety profiles with no muscle decreasing.© 2025 WILEY‐VCH GmbH