Structural Transformative Antioxidants for Dual-Responsive Anti-Inflammatory Delivery and Photoacoustic Inflammation Imaging.
Structural Transformative Antioxidants for Dual-Responsive Anti-Inflammatory Delivery and Photoacoustic Inflammation Imaging.
复制标题
DOI：
10.1002/anie.202100873
复制
发表时间：
2021-04
影响因子：
--
通讯作者：
Caiyan Zhao;Jingxiao Chen;Jiamin Ye;Zhi Li;Lichao Su;Junqing Wang;Ye Zhang;Jinghua Chen
中科院分区：
文献类型：
--
作者：
Caiyan Zhao;Jingxiao Chen;Jiamin Ye;Zhi Li;Lichao Su;Junqing Wang;Ye Zhang;Jinghua Chen
炎症由多种致病因素介导，包括升高的活性氧（ROS）。糖皮质激素被广泛用于减轻许多疾病的炎症，但其生物利用度受到快速代谢、水溶性差和有害副作用的限制。我们在这里合成了一种聚乙二醇化的，苯基硼酸修饰的L-DOPA前抗氧化剂（pPAD），它可以自组装成纳米颗粒（pPADN），用于通过1，3-二醇/苯基硼酸化学和疏水相互作用加载模型糖皮质激素地塞米松（Dex），以更有效地治疗炎症。在暴露于ROS时，pPADN转化为L-DOPA的活性形式，随后通过级联氧化反应转化为抗氧化黑色素样物质。伴随地，pPADN的结构转化触发Dex的特异性释放，沿着炎性组织的酸性pH。在大鼠骨关节炎模型中，Dex负载的pPADN显著减轻滑膜炎症，抑制关节破坏和软骨基质降解，体内毒性可忽略不计。此外，原位结构转换使pPADN适合作为光声成像造影剂的治疗效果的非侵入性监测。总的来说，这种基于抗氧化pPADN的双重应答抗炎递送系统为炎症性疾病提供了精确和有效的治疗诊断策略。
Inflammation is mediated by various pathogenic factors including elevated reactive oxygen species (ROS). Glucocorticoids are widely used to reduce inflammation in many diseases, but their bioavailability is limited by rapid metabolism, poor water-solubility, and harmful side-effects. We here synthesize a PEGylated, phenylboronic acid-modified L-DOPA pro-antioxidant (pPAD) that can self-assemble into nanoparticles (pPADN) for loading of a model glucocorticoid dexamethasone (Dex) through 1,3-diol/phenylboronic acid chemistry and hydrophobic interaction for more effective treatment of inflammation. Upon exposure to ROS, pPADN convert into the active form of L-DOPA, followed by a cascade of oxidative reactions to transform into antioxidative melanin-like materials. Concomitantly, the structural transformation of pPADN triggers 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. Overall, this antioxidative pPADN-based dual-responsive anti-inflammatory delivery system offers a precise and potent theranostic strategy for inflammatory diseases.