The excessive depositions of β-amyloid (Aβ) and abnormal level of reactive oxygen species (ROS) are considered as the important pathogenic factors of Alzheimer’s disease (AD). Strategies targeting only one of them have no obvious effects in clinic. In this study, a multifunctional nanocarrier CICe@M-K that crosses the blood–brain barrier (BBB) efficiently was developed for inhibiting Aβ aggregation and scavenging ROS synchronously. Antioxidant curcumin (Cur) and photosensitizer IR780 were loaded in mesoporous silica nanomaterials (MSNs). Their surfaces were grafted with cerium oxide nanoparticles (CeO₂ NPs) and a short peptide K (CKLVFFAED). Living imaging showed that CICe@M-K was mainly distributed in the brain, liver, and kidneys, indicating CICe@M-K crossed BBB efficiently and accumulated in brain. After the irradiation of 808 nm laser, Cur was continuously released. Both of Cur and the peptide K can recognize and bind to Aβ through multiple interaction including π–π stacking interaction, hydrophobic interaction, and hydrogen bond, inhibiting Aβ aggregation. On the other hand, Cur and CeO₂ NPs cooperate to relieve the oxidative stress in the brains by scavenging ROS. In vivo assays showed that the CICe@M-K could diminish Aβ depositions, alleviate oxidative stress, and improve cognitive ability of the APP/PS1 AD mouse model, which demonstrated that CICe@M-K is a potential agent for AD treatment.

中文翻译：

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多功能纳米载体通过抑制β-淀粉样蛋白聚集和清除活性氧协同治疗阿尔茨海默病


β-淀粉样蛋白（Aβ）的过度沉积和活性氧（ROS）水平的异常被认为是阿尔茨海默病（AD）的重要致病因素。仅针对其中一种的策略在临床上没有明显效果。在这项研究中，开发了一种能够有效穿过血脑屏障（BBB）的多功能纳米载体CICe@M-K，用于同步抑制Aβ聚集和清除ROS。将抗氧化剂姜黄素 (Cur) 和光敏剂 IR780 负载在介孔二氧化硅纳米材料 (MSN) 中。它们的表面接枝有氧化铈纳米粒子（CeO ₂ NPs）和短肽K（CKLVFFAED）。活体成像显示CICe@M-K主要分布在大脑、肝脏和肾脏，表明CICe@M-K能有效穿过血脑屏障并在大脑中积累。 808 nm激光照射后，Cur不断释放。 Cur和肽K均可通过π-π堆积相互作用、疏水相互作用、氢键等多种相互作用识别并结合Aβ，抑制Aβ聚集。另一方面，Cur和CeO ₂ NPs协同通过清除ROS来缓解大脑中的氧化应激。体内实验表明，CICe@M-K 可以减少 Aβ 沉积，减轻氧化应激，并提高 APP/PS1 AD 小鼠模型的认知能力，这表明 CICe@M-K 是治疗 AD 的潜在药物。