Natural Cell Patches: Melanin Nanoparticles for MR Imaging-Guided Antiatherosclerosis Therapy via Attenuating Macrophage Pyroptosis

被引：4

作者：

Zu, Ziyue ^{[1
]}

Sheng, Jie ^{[1
]}

Qi, Jianchen ^{[1
]}

Miao, Yu ^{[2
]}

Zhang, Yunming ^{[1
]}

Zheng, Tao ^{[1
]}

Xiang, Kaiyan ^{[1
]}

Wu, Haoguang ^{[1
]}

Lu, Guangming ^{[1
]}

Zhang, Longjiang ^{[1
]}

机构：

[1] Nanjing Univ, Affiliated Jinling Hosp, Dept Radiol, Med Sch, Nanjing 210002, Peoples R China

[2] Nanjing Univ, Sch Environm, State Key Lab Pollut Control & Resource Reuse, Nanjing 210093, Peoples R China

来源：

ADVANCED FUNCTIONAL MATERIALS | 2023年 / 33卷 / 13期

关键词：

atherosclerosis; melanin nanoparticles; MR imaging; pyroptosis; theranostics; NLRP3; INFLAMMASOME; AUTOPHAGY; POLYPHENOLS; PATHWAY; DEATH; AORTA;

D O I：

10.1002/adfm.202212748

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Pyroptosis, 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-1 beta, interleukin-6, and tumor necrosis factor-alpha). 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 T-1-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.

引用

页数：16