Affiliation:
1. Department of Radiology Affiliated Jinling Hospital Medical School of Nanjing University Nanjing 210002 P. R. China
2. State Key Laboratory of Pollution Control and Resource Reuse School of the Environment Nanjing University Nanjing 210093 P. R. China
Abstract
AbstractPyroptosis, characterized by inflammasome activation, membrane Gasdermin D (GSDMD)‐pore formulation, and the rapid release of inflammatory cytokines, can induce plaque instability and atherosclerosis progression. Nevertheless, insights into the precise antiatherosclerosis therapies targeting pyroptosis remain limited. Here, a novel biomedical application of natural polyphenol melanin as a theranostic antipyroptosis defense nanoplatform for atherosclerosis is reported. Ultrasmall melanin nanoparticles are easily fabricated and functionalized with cyclo‐Arg‐Gly‐Asp‐d‐Tyr‐Lys conjugated polyethylene glycol to yield cRGD‐PEG‐MNPs (RpMPs) to target plaque neovascularization, which is confirmed by fluorescence imaging. Importantly, RpMPs act like cell patches to suppress pyroptosis in lipopolysaccharide‐stimulated macrophages by scavenging reactive oxygen species, downregulating the expression levels of pyroptosis‐related proteins (NLRP3, Caspase 1, and GSDMD) and reducing the leakage of inflammatory cytokines (interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α). In vivo studies further reveal that RpMPs can ameliorate the development and improve the stability of atherosclerotic plaques via attenuating NLRP3‐stimulated pyroptosis and inducing an anti‐inflammatory phenotype in the aorta of ApoE−/− mice. Moreover, chelator‐free Gd3+‐RpMPs exhibit persistent T1‐weighted contrast‐enhanced efficiency and plaque resident on a 9.4 T Micro magnetic resonance scanner in murine atherosclerosis model. Overall, this study suggests the potential for using melanin to develop natural multifunctional nanoplatforms for molecular theranostic in atherosclerosis and other pyroptosis‐related diseases.
Funder
National Key Research and Development Program of China
Fundamental Research Funds for the Central Universities
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials
Cited by
3 articles.
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