Hypoxia-Activated Probe for Targeted Photoacoustic Imaging and Photothermal Modulation of Adipose Tissue in Obesity

Obesity, characterized by the persistent expansion of adipose tissue (AT), has become a major global health burden, necessitating the development of safe and effective therapeutic approaches to restore AT function. In this study, we utilize the enhanced hypoxic microenvironment of AT to develop a hypoxia-activated phototheranostic probe for obesity management. Caging Aza-BODIPY fluorophore (CBH) with a unique N-oxide group yields a hypoxic-responsive probe (CBH-O). Intraperitoneal injection of CBH-O formulated nanoparticles (CBH-O NPs) in obese mice enables targeted photoacoustic imaging of visceral AT, accompanied by the generation of CBH NPs with a high photothermal conversion efficiency. Photothermal modulation of visceral AT can induce white AT browning, enhance lipolysis, and alleviate inflammation, leading to a reduction of body weight (15.6%) and AT mass (65%), a decrease of cholesterol (49.1%), triglyceride (30.3%), and insulin (75.7%) in serum, a decrease in pro-inflammatory markers (IL-6, MCP-1), and an increase of the anti-inflammatory marker (IL-10). This AT hypoxic-microenvironment-responsive therapeutic strategy provides a novel and practical approach for managing obesity and its associated metabolic complications.