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

Abstract

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 nano-antioxidants 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 O2•−, H2O2, •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 their effective protection of ischemic brains with negligible side effects.

Dark- or Light-Colored Melanins: Generating Pigments Using Fe2+ and H2O2

“…Our results do suggest that, depending on the intensity of the oxidative reaction, chemically-distinct, dark-or light-colored MN-like pigments could be generated depending on the type of precursor that is present. Such physically and chemically distinct MN materials could find different applications 7,16,[43][44][45][46] or possess different cell-biological properties [47][48][49][50][51][52] In addition, our results suggest that the absence of a dark color does not necessarily mean the absence of MN-like materials which may have implications for the evaluation of histological or fossil specimens. [53][54] …”

Reactive Oxygen Species‐Responsive Nanoparticles for the Treatment of Ischemic Stroke

“…[10][11][12][13][14][15] However, low molecular weight antioxidants (for instance NXY-059) have historically not translated well in the treatment of stroke patients. [19] They also showed in a rat model of ischemic stroke that MeNPs reduce brain superoxide levels and infarct volume. [16][17][18] For example, Liu and colleagues have demonstrated that melanin NPs (MeNPs) scavenge multiple reactive oxygen and nitrogen species (RONS), suppress RONS-induced inflammation, and are neuroprotective in vitro.…”

A Bacteriochlorin‐Based Metal–Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging‐Guided Highly Efficient Photodynamic Therapy

“…[20][21][22] It reacts with proteins, DNA, or lipids, to achieve irreversible cellular components damage and dysfunction in cell metabolism and even cell apoptosis. [24][25][26] The accumulated H 2 O 2 further transforms into highly cytotoxic hydroxyl radical (OH•) to significantly aggravate the oxidative damage and enhance PDT anticancer efficiency. [24][25][26] The accumulated H 2 O 2 further transforms into highly cytotoxic hydroxyl radical (OH•) to significantly aggravate the oxidative damage and enhance PDT anticancer efficiency.…”