Structural Transformative Antioxidants for Dual‐Responsive Anti‐Inflammatory Delivery and Photoacoustic Inflammation Imaging. Issue 26 (11th May 2021)

• Record Type: Journal Article
• Authors: Zhao, Caiyan; Chen, Jingxiao; Ye, Jiamin; Li, Zhi; Su, Lichao; Wang, Junqing; Zhang, Ye; Chen, Jinghua; Yang, Huanghao; Shi, Jinjun; Song, Jibin
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 26(2021)
• Page Start: 14458
• Page End: 14466
• Publication Date: 2021-05-11
• Subjects: antioxidants -- drug delivery -- inflammation -- L-DOPA -- photoacoustic imaging; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202100873
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : PEGylated, phenylboronic acid modified L‐DOPA‐derived nanoparticles (pPADN) specifically integrated reactive oxygen species (ROS) scavenging and anti‐inflammatory drug delivery to treat osteoarthritis. The pPADN sensed and eliminated elevated ROS via cascade oxidative reactions and delivered glucocorticoids to the site of inflammation.