Structural Transformative Antioxidants for Dual‐Responsive Anti‐Inflammatory Delivery and Photoacoustic Inflammation Imaging

Abstract We have synthesized a PEGylated, phenylboronic acid modified L‐DOPA pro‐antioxidant (pPAD) that can self‐assemble into nanoparticles (pPADN) for the loading of a model glucocorticoid dexamethasone (Dex) through 1,3‐diol/phenylboronic acid chemistry and hydrophobic interactions for more effective treatment of inflammation. Upon exposure to ROS, pPADN convert into the active form of L‐DOPA, and a cascade of oxidative reactions transform it into antioxidative melanin‐like materials. Concomitantly, the structural transformation of pPADN triggers the specific release of Dex, along with the acidic pH of inflammatory tissue. In a rat model of osteoarthritis, Dex‐loaded pPADN markedly mitigate synovial inflammation, suppress joint destruction and cartilage matrix degradation, with negligible in vivo toxicity. Moreover, in situ structural transformation makes pPADN suitable for noninvasive monitoring of therapeutic effects as a photoacoustic imaging contrast agent.