Unlocking the potential of metal nanoparticles (NPs) in biomedical applications represents a leading endeavor in contemporary research. Among these, gold NPs (AuNPs) and silver NPs (AgNPs) have shown promising strides in combatting complex neurodegenerative ailments like Alzheimer’s disease. Yet, the unexplored realm of bimetallic Au/Ag-NP harbors immense potential, concealing undiscovered opportunities for enhanced therapeutic effectiveness through the synergistic interaction of metal ions. Nonetheless, the limitations of traditional synthesis methods have restricted the preparation, biocompatibility, and versatility of these NPs, prompting an urgent requirement for innovative approaches. Biobased synthetic methodologies have emerged as a noteworthy solution to address these challenges. Our study ventures into uncharted terrain, harnessing collagen-mimicking peptide nanofibers as a bioactive template for the synthesis of bimetallic NPs. These green NPs exhibit remarkable activity in inhibiting amyloid β (Aβ) protein aggregation with almost 74% inhibition, surpassing the individual impacts of Au and Ag NPs, which show inhibition percentages of 66 and 43, respectively. The bimetallic Au/Ag-NPs not only demonstrate powerful inhibition of Aβ, but they also demonstrate inhibitory activity against esterase (∼50%) and against reactive oxygen species (ROS) (∼75%), metamorphosing into multifaceted therapeutic agents for Alzheimer’s disease. Au/Ag-NPs have proven highly beneficial in surpassing cellular barriers, as evidenced by studies on tissue penetration, 3D uptake, and endosomal escape, and these attributes also hold promise for the future treatment modalities. The findings indicate that the intrinsic traits of Au/Ag-NPs provide numerous mechanistic benefits, such as inhibiting Aβ and acetylcholinesterase (AChE), and reducing stress related to ROS, in addition to their advantageous internalization properties. This research represents a notable advancement in the development of multitargeted treatments for neurodegenerative disorders using bimetallic NPs, diverging from the prevalent emphasis on AuNPs in the current literature.

中文翻译：

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探索双金属纳米颗粒在阿尔茨海默病治疗中的应用：一种具有多靶点潜力的新型生物辅助合成

释放金属纳米粒子 (NP) 在生物医学应用中的潜力代表了当代研究的领先努力。其中，金纳米颗粒 (AuNP) 和银纳米颗粒 (AgNP) 在对抗阿尔茨海默病等复杂的神经退行性疾病方面已显示出可喜的进展。然而，双金属 Au/Ag-NP 的未开发领域蕴藏着巨大的潜力，隐藏着通过金属离子的协同相互作用增强治疗效果的未被发现的机会。尽管如此，传统合成方法的局限性限制了这些纳米颗粒的制备、生物相容性和多功能性，迫切需要创新方法。生物基合成方法已成为应对这些挑战的一个值得注意的解决方案。我们的研究进入了未知领域，利用模拟胶原蛋白肽纳米纤维作为合成双金属纳米颗粒的生物活性模板。这些绿色纳米颗粒在抑制β淀粉样蛋白 (Aβ) 蛋白聚集方面表现出显着的活性，抑制率接近 74%，超过了金纳米颗粒和银纳米颗粒的单独影响，后者的抑制百分比分别为 66 和 43。双金属 Au/Ag-NP 不仅表现出对 Aβ 的强大抑制作用，而且还表现出对酯酶 (∼50%) 和活性氧 (ROS) (∼75%) 的抑制活性，可转变为阿尔茨海默病的多方面治疗剂。组织渗透、3D 摄取和内体逃逸的研究证明，Au/Ag-NP 在突破细胞屏障方面非常有益，这些特性也为未来的治疗方式带来了希望。研究结果表明，Au/Ag-NPs 的内在特性除了具有有利的内化特性外，还提供了许多机械益处，例如抑制 Aβ 和乙酰胆碱酯酶 (AChE)，以及减少与 ROS 相关的应激。这项研究代表了使用双金属纳米颗粒开发多靶点治疗神经退行性疾病的显着进展，与当前文献中普遍强调的金纳米颗粒不同。