Photoacoustic Imaging‐Guided Self‐Adaptive Hyperthermia Supramolecular Cascade Nano‐Reactor for Diabetic Periodontal Bone Regeneration

Abstract Commencing with the breakdown of the diabetic osteoimmune microenvironment, multiple pathogenic factors, including hyperglycemia, inflammation, hypoxia, and deleterious cytokines, are conjointly involved in the progression of diabetic periodontal bone regeneration. Based on the challenge of periodontal bone regeneration treatment and the absence of real‐time feedback of blood oxygen fluctuation in diabetes mellitus, a novel self‐adaptive hyperthermia supramolecular cascade nano‐reactor ACFDG is constructed via one‐step supramolecular self‐assembly strategy to address multiple factors in diabetic periodontal bone regeneration. Hyperthermia supramolecular ACFDG possesses high photothermal conversion efficiency (32.1%), and it can effectively inhibit the vicious cycle of ROS‐inflammatory cascade through catalytic cascade reactions, up‐regulate the expression of heat shock proteins (HSPs) under near‐infrared (NIR) irradiation, which promotes periodontal bone regeneration. Remarkably, ACFDG can provide real‐time non‐invasive diagnosis of blood oxygen changes during periodontal bone regeneration through photoacoustic (PA) imaging, thus can timely monitor periodontal hypoxia status. In conclusion, this multifunctional supramolecular nano‐reactor combined with PA imaging for real‐time efficacy monitoring provides important insights into the biological mechanisms of diabetic periodontal bone regeneration and potential clinical theranostics.