Hypoxia-Activated Probe for Targeted Photoacoustic Imaging and Photothermal Modulation of Adipose Tissue in Obesity
Long Xiao1, Rui Li1, Xingyu Zhu1
1School of Life Science and Medical Engineering, State Key Laboratory of Optoelectronic Information Acquisition and Protection Technology, Key Laboratory of Structure and Functional Regulation of Hybrid Materials of Ministry of Education, Anhui University, Hefei, Anhui 230601, China.
Abstract:
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.
