Hydrogels Treat Atopic Dermatitis by Transporting Marine-Derived miR-100-5p-Abundant Extracellular Vesicles.

IF 5.4 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Biomaterials Science & Engineering Pub Date : 2024-11-25 DOI:10.1021/acsbiomaterials.4c01649

Zijie Wu, Lei He, Linhong Yan, Baoyi Tan, Lihua Ma, Guoli He, Zhenqing Dai, Ruikun Sun, Chengyong Li

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Abstract

Atopic dermatitis (AD) is a prevalent skin disorder worldwide. However, many AD medications are unsuitable for long-term use due to low therapeutic efficacy and side effects. Extracellular vesicles (EVs) extracted from Pinctada martensii mucus have demonstrated therapeutic efficacy in AD. It is hypothesized that EVs may exert their activity on mammalian cells through their specific contents. In this study, we analyzed the results of miRNA sequencing of the EVs and investigated the potency of highly expressed miR-100-5p in treating AD. To enhance the therapeutic efficiency of the EVs in AD, we developed oxidized sodium alginate (OSA)-carboxymethyl chitosan (CMCS) self-cross-linked hydrogels as a vehicle to deliver the EVs to BALB/c mice with dermatitis. The miR-100-5p in EVs exhibited a favorable anti-inflammatory function, while the hydrogels provided enhanced skin residency. Additionally, its efficacy in inflammation inhibition and collagen synthesis was demonstrated in in vivo experiments. Mechanistically, miR-100-5p in EVs exerted anti-inflammatory effects by inhibiting the expression of FOXO3, consequently suppressing the activation of the downstream NLRP3 signaling pathway. This study underscores the significance of utilizing OSA-CMCS hydrogels as a vehicle for delivering miR-100-5p in P. martensii mucus-derived EVs for the treatment of AD.

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水凝胶通过运输海洋衍生的大量 miR-100-5p 细胞外小泡治疗特应性皮炎

特应性皮炎（AD）是一种全球流行的皮肤疾病。然而，由于疗效低和副作用大，许多特应性皮炎药物不适合长期使用。从貂皮粘液中提取的细胞外囊泡（EVs）已证明对AD有疗效。据推测，EVs 可能通过其特定内容物对哺乳动物细胞发挥活性。在本研究中，我们分析了 EVs 的 miRNA 测序结果，并研究了高表达 miR-100-5p 对治疗 AD 的有效性。为了提高EVs对AD的治疗效果，我们开发了氧化海藻酸钠（OSA）-羧甲基壳聚糖（CMCS）自交联水凝胶作为载体，将EVs输送给患有皮炎的BALB/c小鼠。EVs中的miR-100-5p表现出了良好的抗炎功能，而水凝胶则增强了皮肤的驻留性。此外，其抑制炎症和胶原蛋白合成的功效也在体内实验中得到了证实。从机理上讲，EVs 中的 miR-100-5p 通过抑制 FOXO3 的表达，从而抑制下游 NLRP3 信号通路的激活来发挥抗炎作用。这项研究强调了利用OSA-CMCS水凝胶作为载体，在貂皮粘液衍生的EVs中递送miR-100-5p以治疗AD的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Biomaterials Science & Engineering Materials Science-Biomaterials

CiteScore

10.30

自引率

3.40%

发文量

413

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