黑色素样纳米颗粒替代视网膜色素上皮细胞中的天然黑色素及其对年龄相关性黄斑变性的治疗作用,ACS Nano

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黑色素样纳米颗粒替代视网膜色素上皮细胞中的天然黑色素及其对年龄相关性黄斑变性的治疗作用
ACS Nano ( IF 15.8 ) Pub Date : 2022-10-21 , DOI: 10.1021/acsnano.2c09087
Yong-Su Kwon ₁ , Min Zheng ₁ , Alice Yang Zhang ₁ , Zongchao Han _{1,

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Affiliation

黑色素是一种天然色素，广泛分布于人体的许多部位，如皮肤和眼睛中的视网膜色素上皮（RPE）。与表皮黑色素细胞不断合成的皮肤黑色素相反，RPE 中的黑色素不会再生。已知黑色素可作为潜在的自由基清除剂和光保护剂。然而，黑色素对氧化应激的保护作用随着年龄的增长而下降。这种现象与年龄相关性黄斑变性 (AMD) 的发病机制相关。为了增加黑色素的潜在抗氧化和光保护特性，我们设计了一种治疗策略，用于在 RPE 中使用聚乙二醇化合成黑色素样纳米粒子 (MNP) 补充黑色素以治疗 AMD。我们使用类似 AMD 的细胞和小鼠模型进行了实验，并证明 MNP 具有生物相容性，并选择性地靶向具有强大抗氧化特性的活性氧 (ROS)。MNPs 可以在 RPE 中运输和积累，并且在单剂量玻璃体内注射后至少 3 个月内仅位于细胞质中，而不是细胞的细胞核和线粒体中。我们的研究结果表明，MNPs 能够替代 RPE 中的天然黑色素，并表明 MNPs 作为天然自由基清除剂在 ROS 相关疾病（如 AMD）中对抗氧化应激的潜在功效。MNPs 可以在 RPE 中运输和积累，并且在单剂量玻璃体内注射后至少 3 个月内仅位于细胞质中，而不是细胞的细胞核和线粒体中。我们的研究结果表明，MNPs 能够替代 RPE 中的天然黑色素，并表明 MNPs 作为天然自由基清除剂在 ROS 相关疾病（如 AMD）中对抗氧化应激的潜在功效。MNPs 可以在 RPE 中运输和积累，并且在单剂量玻璃体内注射后至少 3 个月内仅位于细胞质中，而不是细胞的细胞核和线粒体中。我们的研究结果表明，MNPs 能够替代 RPE 中的天然黑色素，并表明 MNPs 作为天然自由基清除剂在 ROS 相关疾病（如 AMD）中对抗氧化应激的潜在功效。

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Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

更新日期：2022-10-21

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