Lin Xiaoding, Dong Xiaoyan, Sun Yan
Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin, 300350, China.
Small. 2024 Dec;20(51):e2407154. doi: 10.1002/smll.202407154. Epub 2024 Oct 11.
The abnormal accumulation of β-amyloid protein (Aβ) is considered as the main pathological hallmark of Alzheimer's disease (AD). The design of potent multifunctional theranostic agents targeting Aβ is one of the effective strategies for AD prevention and treatment. Nanomotors as intelligent, advanced, and multifunctional nanoplatforms can perform many complex tasks, but their application in AD theranostics is rare. Herein, sub-10nm multifunctional dual-carbon dots composites (ERCD) with photo-propelled nanomotor behavior are fabricated by conjugating near-infrared (NIR) carbon dots (RCD) of thermogenic and photodynamic capability with the previously reported epigallocatechin gallate-derived carbonized polymer dots (ECD). ERCD-1 (ECD:RCD = 1:2.5) showed potent inhibitory capability similar to ECD in the absence of NIR light, and exhibited photooxygenation activity and nanomotor behavior powered by "self-thermophoretic force" under NIR irradiation, significantly enhancing the inhibition, disaggregation, and photooxygenation capabilities. The nanomotor suppressed Aβ fibrillization and rapidly disaggregated mature Aβ fibrils at very low concentrations (0.5 µg mL). Moreover, the NIR-activated ERCD-1 imaged Aβ plaques in vivo and prolonged nematode lifespan by 6 d at 2 µg mL. As a proof-of-concept, this work opened a new avenue to the design of multifunctional sub-10nm nanomotors targeting Aβ for AD theranostics.
β-淀粉样蛋白(Aβ)的异常积累被认为是阿尔茨海默病(AD)的主要病理标志。设计靶向Aβ的高效多功能诊疗试剂是AD预防和治疗的有效策略之一。纳米马达作为智能、先进且多功能的纳米平台,可以执行许多复杂任务,但其在AD诊疗中的应用却很少见。在此,通过将具有产热和光动力能力的近红外(NIR)碳点(RCD)与先前报道的表没食子儿茶素没食子酸酯衍生的碳化聚合物点(ECD)共轭,制备了具有光驱动纳米马达行为的亚10纳米多功能双碳点复合材料(ERCD)。在没有近红外光的情况下,ERCD-1(ECD:RCD = 1:2.5)表现出与ECD相似的强大抑制能力,并且在近红外照射下表现出光氧化活性和由“自热泳力”驱动的纳米马达行为,显著增强了抑制、解聚和光氧化能力。该纳米马达在极低浓度(0.5 μg mL)下抑制Aβ纤维化并迅速解聚成熟的Aβ纤维。此外,近红外激活的ERCD-1在体内对Aβ斑块进行成像,并在2 μg mL时将线虫寿命延长了6天。作为概念验证,这项工作为设计用于AD诊疗的靶向Aβ的多功能亚10纳米纳米马达开辟了一条新途径。
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