Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
Department of Biochemical Engineering, School of Chemical Engineering and Technology and Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
Acta Biomater. 2022 Aug;148:298-309. doi: 10.1016/j.actbio.2022.06.029. Epub 2022 Jun 19.
The complex pathogenesis of Alzheimer's disease (AD) involves the aggregation and accumulation of amyloid β-protein (Aβ) as well as elevated levels of reactive oxygen species (ROS), which requires the development of comprehensive diagnostic and therapeutic interventions. In this work, a multifunctional theranostic nano-composite (HSA-BFP@CDs) is constructed by conjugating triple-functionalized human serum albumin (HSA-BFP) as a theranostic agent targeting Aβ and carbon dots (CDs) as an ROS scavenger. HSA-BFP@CDs exhibits a fluorescence "off-on" effect at 700 nm upon interaction with Aβ aggregates, showing the capability for detection of Aβ plaques and potential for early diagnosis of AD. Besides, HSA-BFP@CDs effectively inhibits the aggregation of Aβ, increasing the viability of Aβ-treated cells from 74% to over 95% at 100 µg/mL. Moreover, multiple ROS, including hydroxyl radicals, superoxide radicals, hydrogen peroxide, and Aβ-Cu-induced-ROS, can be scavenged by HSA-BFP@CDs, thus resulting in the mitigation of cellular oxidative damages. Experiments with the AD model of Caenorhabditis elegans further demonstrate the multifunctionality of HSA-BFP@CDs in imaging amyloid plaques, reducing Aβ deposition, and relieving oxidative stress in vivo, showing the prospect for Aβ- and ROS-targeted AD diagnosis and treatment. This work provided new insight into the design of protein-carbon dots conjugate and the development of multi-target therapy of AD. STATEMENT OF SIGNIFICANCE: Alzheimer's disease (AD) is the most common form of dementia, which currently affects over 55 million people worldwide. Due to the complex pathogenesis of AD involving amyloid β-protein (Aβ) aggregation as well as elevated levels of reactive oxygen species (ROS), it is highly desired to develop comprehensive diagnostic and therapeutic interventions. In this paper, we fabricated a multifunctional theranostic nano-composite (HSA-BFP@CDs) via the conjugation of triple-functionalized human serum albumin (HSA-BFP) and carbon dots (CDs). The multifunctionality of HSA-BFP@CDs for efficient detection of Aβ aggregates and inhibition of Aβ aggregation as well as scavenging of ROS was demonstrated, demonstrating the potential of the protein-carbon dots conjugate for the multi-target therapy of AD.
阿尔茨海默病（AD）的复杂发病机制涉及淀粉样β蛋白（Aβ）的聚集和积累以及活性氧（ROS）水平的升高，这需要开发全面的诊断和治疗干预措施。在这项工作中，通过将三重功能化的人血清白蛋白（HSA-BFP）与碳点（CDs）偶联，构建了一种多功能治疗纳米复合材料（HSA-BFP@CDs）。HSA-BFP@CDs 在与 Aβ 聚集体相互作用时，在 700nm 处表现出荧光“关-开”效应，显示了检测 Aβ 斑块的能力和 AD 早期诊断的潜力。此外，HSA-BFP@CDs 还能有效抑制 Aβ 的聚集，使 Aβ 处理细胞的存活率从 74%提高到 100μg/ml 以上的 95%以上。此外，HSA-BFP@CDs 可以清除多种 ROS，包括羟基自由基、超氧自由基、过氧化氢和 Aβ-Cu 诱导的 ROS，从而减轻细胞氧化损伤。利用秀丽隐杆线虫 AD 模型的实验进一步证明了 HSA-BFP@CDs 在体内成像淀粉样斑块、减少 Aβ 沉积和缓解氧化应激方面的多功能性，为 Aβ 和 ROS 靶向 AD 诊断和治疗提供了前景。这项工作为设计蛋白质-碳点偶联物和开发 AD 的多靶点治疗提供了新的思路。
意义声明：阿尔茨海默病（AD）是最常见的痴呆症形式，目前全球有超过 5500 万人受其影响。由于 AD 的发病机制复杂，涉及 Aβ 聚集以及活性氧（ROS）水平升高，因此非常需要开发全面的诊断和治疗干预措施。在本文中，我们通过三重功能化人血清白蛋白（HSA-BFP）和碳点（CDs）的偶联，制备了一种多功能治疗纳米复合材料（HSA-BFP@CDs）。证明了 HSA-BFP@CDs 具有高效检测 Aβ 聚集体和抑制 Aβ 聚集以及清除 ROS 的多功能性，表明该蛋白-碳点偶联物在 AD 的多靶点治疗中有很大的潜力。
