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基于连接网络的高表面暴露 Ru 位点的人工抗氧化酶用于高效调节微环境和缓解光致性皮炎。

Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis.

机构信息

Department of Medical Ultrasound, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.

出版信息

ACS Nano. 2024 Jan 30;18(4):3424-3437. doi: 10.1021/acsnano.3c10552. Epub 2024 Jan 16.

DOI:10.1021/acsnano.3c10552
PMID:38227828
Abstract

Solar dermatitis, a form of acute radiation burn that affects the skin, results from overexposure to ultraviolet B (UVB) radiation in strong sunlight. Cell damage caused by the accumulation of reactive oxygen species (ROS) produced by UVB radiation plays an important role in UVB-induced inflammation in the skin. Here, for efficiently scavenging excess ROS, modulating the microenvironment, and alleviating solar dermatitis, a π-conjugated network polyphthalocyanine supporting a highly surface-exposed Ru active site-based artificial antioxidase (HSE-PPcRu) is designed and fabricated with excellent ROS-scavenging, antioxidant, and anti-inflammatory capabilities. In photodamaged human keratinocyte cells, HSE-PPcRu could modulate mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B signaling pathways, prevent DNA damage, suppress apoptosis, inhibit pro-inflammatory cytokine secretion, and alleviate cell damage. animal experiments reveal the higher antioxidant and anti-inflammatory efficacies of HSE-PPcRu by reversing the activation of p38 and c-Jun N-terminal kinase, inhibiting expression of cyclooxygenase-2, interleukin-6, interleukin-8, and tumor necrosis factor-α. This work not only provides an idea for alleviating solar dermatitis via catalytically scavenging ROS and modulating the microenvironment but also offers a strategy to design an intelligent conjugated network-based artificial antioxidase with a highly surface-exposed active site.

摘要

光化性皮炎是一种影响皮肤的急性辐射灼伤,是由于过度暴露于强阳光中的中波紫外线 (UVB) 辐射而引起的。UVB 辐射产生的活性氧(ROS)的积累所导致的细胞损伤,在皮肤的 UVB 诱导炎症中起着重要作用。在这里,为了有效地清除过量的 ROS、调节微环境并缓解光化性皮炎,设计并制备了一种具有优异 ROS 清除、抗氧化和抗炎能力的π-共轭网络多酞菁支持高度暴露于表面的钌活性位点的人工抗氧化酶(HSE-PPcRu)。在光损伤的人角质形成细胞中,HSE-PPcRu 可以调节丝裂原活化蛋白激酶(MAPK)和核因子κB 信号通路,防止 DNA 损伤,抑制细胞凋亡,抑制促炎细胞因子的分泌,并减轻细胞损伤。动物实验通过逆转 p38 和 c-Jun N 末端激酶的激活、抑制环加氧酶-2、白细胞介素-6、白细胞介素-8 和肿瘤坏死因子-α的表达,揭示了 HSE-PPcRu 更高的抗氧化和抗炎功效。这项工作不仅提供了一种通过催化清除 ROS 和调节微环境来缓解光化性皮炎的思路,而且还提供了一种设计具有高度暴露表面活性位点的智能共轭网络基人工抗氧化酶的策略。

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