Department of Dermatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Institute for Regenerative Medicine, Institute for Translational Nanomedicine, Shanghai East Hospital, Tongji University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2024 Aug 27;19:8779-8796. doi: 10.2147/IJN.S472999. eCollection 2024.
Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease.
HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed.
Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation.
Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.
特应性皮炎（AD）是一种可影响各年龄段人群的慢性炎症性皮肤病。最近的研究表明，氧化应激在 AD 的发展中起着关键作用。因此，抑制氧化应激可能是 AD 的一种有效治疗方法。纳米钼是一种有前途的抗氧化剂材料。我们旨在通过使用化学诱导的 AD 样疾病的小鼠模型来评估钼纳米粒子（Mo NPs）的治疗效果和初步机制。
HaCaT 细胞是一种自发永生化的人角质形成细胞系，在用 Mo NPs 预处理后，由肿瘤坏死因子-α/干扰素-γ刺激。然后评估活性氧水平、炎症因子的产生以及核因子 kappa-B 和核因子红系 2 相关因子途径的激活。Mo NPs 被局部应用于 MC903 诱导的 AD 样疾病小鼠模型中，MC903 是一种维生素 D3 类似物。评估皮炎评分、瘙痒评分、经表皮水分丢失和体重。评估与 AD 相关的炎症因子和趋化因子。评估核因子 kappa-B 和核因子红系 2 相关因子/血红素加氧酶-1 途径的激活。
我们的数据表明，Mo NPs 分散体的局部应用可以显著缓解 AD 皮肤损伤和瘙痒，并促进皮肤屏障修复。进一步的机制实验表明，Mo NPs 可以抑制核因子 kappa-B 途径的过度激活，促进核因子红系 2 相关因子和血红素加氧酶-1 蛋白的表达，并抑制氧化应激反应。此外，它们抑制胸腺基质淋巴细胞生成素、炎症因子和趋化因子的表达，从而缓解皮肤炎症。
Mo NPs 为 AD 患者提供了一种有前途的替代治疗选择，因为它们可以同时解决 AD 发病机制中的三个关键机制。
