老年痴呆症（AD）是老年期最常见的神经退行性疾病。β-淀粉样肽（Aβ）的积累和线粒体功能障碍导致持续的小胶质细胞激活，加剧神经炎症并促进神经退行。小胶质细胞是大脑和脊髓的驻留巨噬细胞，通过一系列表型维持大脑内稳态的重要作用，包括促炎症表型和抗炎症表型。然而，持续激活的小胶质细胞会产生活性氧化物和神经毒性介质。因此，小胶质细胞激活抑制剂被认为对AD治疗有潜力。修改的TPP/MoS2量子点混合物是一种以线粒体为靶标的纳米材料，通过清除自由基发挥细胞保护作用和抗氧化特性。在本研究中，研究了Aβ刺激的小胶质细胞上DSPE-PEG-TPP/MoS2量子点混合物的细胞存活率和细胞毒性。同时评估了活性氧化物（ROS）和线粒体膜电位（MMP）的水平。此外，在存在或不存在DSPE-PEG-TPP/MoS2量子点混合物的情况下，测量了小胶质细胞活化所致Aβ积累的不可逆转模拟小胶质细胞的前炎症因子和抗炎因子（如肿瘤坏死因子α（TNF-α），白细胞介素-6（IL-6），白细胞介素-1β（IL-1β），转化生长因子β（TGF-β），可诱导型一氧化氮合酶（iNOS）和精氨酸酶-1（Arg-I））。我们发现DSPE-PEG-TPP/MoS2量子点混合物在特定浓度下具有生物相容性和无毒性。此外，修饰的TPP/MoS2量子点混合物能够显著降低游离基的释放量，并通过提高MMP对Aβ刺激的小胶质细胞的线粒体功能进行剂量依赖性改善。此外，在Aβ刺激前以25和50μg/mL浓度预处理小胶质细胞，能够显著抑制IL-1β，IL-6，TNF-α和iNOS等前炎症因子的释放和表达。然而，抗炎因子TGF-β和Arg-I被激活。这些发现表明修饰的TPP/MoS2量子点混合物能够减少Aβ刺激的不可逆转模拟小胶质细胞中的氧化应激，炎症反应并改善线粒体功能。总体而言，我们的研究表明DSPE-PEG-TPP/MoS2量子点混合物在AD管理方面具有治疗潜力，并影响小胶质细胞极化。

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of β-amyloid peptide (Aβ) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators. Therefore, inhibitors of microglial activation are seen to have promise in AD control. The modified TPP/MoS2 QD blend is a mitochondrion-targeted nanomaterial that exhibits cytoprotective activities and antioxidant properties through scavenging free radicals. In the present study, the cell viability and cytotoxicity of the DSPE-PEG-TPP/MoS2 QD blend on microglial cells stimulated by Aβ were investigated. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also assessed. In addition, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), transforming growth factor beta (TGF-β), inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-I) were measured in the presence or absence of the DSPE-PEG-TPP/MoS2 QD blend on an immortalized microglia cells activated by accumulation of Aβ. We found that the DSPE-PEG-TPP/MoS2 QD blend was biocompatible and nontoxic at specific concentrations. Furthermore, the modified TPP/MoS2 QD blend significantly reduced the release of free radicals and improved the mitochondrial function through the upregulation of MMP in a dose-dependent manner on microglial cells treated with Aβ. In addition, pre-treatment of microglia with the DSPE-PEG-TPP/MoS2 QD blend at concentrations of 25 and 50 μg/mL prior to Aβ stimulation significantly inhibited the release and expression of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α, and iNOS. Nevertheless, the anti-inflammatory cytokines TGF-β and Arg-I were activated. These findings suggest that the modified TPP/MoS2 QD blend reduced oxidative stress, inflammation and improved the mitochondrial function in the immortalized microglial cells (IMG) activated by Aβ. Overall, our research shows that the DSPE-PEG-TPP/MoS2 QD blend has therapeutic promise for managing AD and can impact microglia polarization.