Injectable NIR-II Photothermal Hydrogels for Image-Guided Adipose Remodeling and Antiobesity Therapy.

Abstract

Obesity is a chronic metabolic disorder associated with severe comorbidities and limited effective treatments, including lifestyle interventions, pharmacotherapies, and bariatric surgery. Photothermal therapy (PTT) offers a noninvasive alternative, yet few photothermal materials enable concurrent therapeutic and imaging functions. Herein, an injectable photothermal hydrogel with fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm) is reported, enabling <i>in situ</i> adipose tissue remodeling through mild, image-guided PTT. A pyrazine-based molecule, PPT-TPA8, was rationally engineered to integrate strong NIR absorption, bright NIR-II emission, and high photothermal stability. Incorporated into a PLGA-PEG-PLGA thermoresponsive matrix, it forms a hydrogel with controllable mild heating and sustained local retention under low-power irradiation. <i>In vitro</i> and <i>in vivo</i> studies show that the hydrogel under NIR irradiation induces adipocyte apoptosis and white-to-beige fat conversion, reducing fat accumulation and improving metabolism without systemic toxicity. Furthermore, NIR-II fluorescence enabled real-time, noninvasive tracking of hydrogel degradation and distribution. This biocompatible, image-guided, and minimally invasive platform provides a promising strategy for precise, localized antiobesity therapy.