Comprehensive Insights into the Multi-Antioxidative Mechanisms of Melanin Nanoparticles and Their Application To Protect Brain from Injury in Ischemic Stroke

作者：Yanlan Liu, Kelong Ai, Xiaoyuan Ji, Diana Askhatova, Rose Du, Lehui Lu, Jinjun Shi · 发表于：Journal of the American Chemical Society · 年份：2016 · DOI：10.1021/jacs.6b11013 · 被引用次数：550 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Neuroinflammation and Neurodegeneration Mechanisms

Nanotechnology-mediated antioxidative therapy is emerging as a novel strategy for treating a myriad of important diseases through scavenging excessive reactive oxygen and nitrogen species (RONS), a mechanism critical in disease development and progression. However, similar to antioxidative enzymes, currently studied nanoantioxidants have demonstrated scavenging activity to specific RONS, and sufficient antioxidative effects against multiple RONS generated in diseases remain elusive. Here we propose to develop bioinspired melanin nanoparticles (MeNPs) for more potent and safer antioxidative therapy. While melanin is known to function as a potential radical scavenger, its antioxidative mechanisms are far from clear, and its applications for the treatment of RONS-associated diseases have yet to be well-explored. In this study, we provide for the first time exhaustive characterization of the activities of MeNPs against multiple RONS including O 2 •–, H 2 O 2, • OH, • NO, and ONOO –, the main toxic RONS generated in diseases. The potential of MeNPs for antioxidative therapy has also been evaluated in vitro and in a rat model of ischemic stroke. In addition to the broad defense against these RONS, MeNPs can also attenuate the RONS-triggered inflammatory responses through suppressing the expression of inflammatory mediators and cytokines. In vivo results further demonstrate that these unique multi-antioxidative, anti-inflammatory, and biocompatible features of MeNPs contribute to th...