β淀粉样蛋白（Aβ）的脑内自聚是阿尔茨海默病（AD）的主要病理特征，因此，以Aβ为靶点的多功能解毒剂开发是AD防治领域的研究热点。本项目提出了设计新型近红外光（NIR）驱动的“基于纳米马达的多功能解毒剂”（NMA）的研究构想。NMA由两面体纳米粒子（JNP）构成，JNP的疏水面键合具有NIR光热效应的金纳米星、亲水面修饰多功能肽抑制剂、内部包埋具有NIR光热效应和Cu2+螯合功能的黒磷量子点（BPQD）。系统研究表面多功能抑制剂的作用、纳米马达对NMA 解毒作用的强化和BPQD光热效应的纤维解聚反应，揭示光热效应对BPQD和纳米马达作用的相互影响，以及NMA作用过程Aβ结构转换、聚集、解聚和Cu2+螯合等反应过程及其相互作用的复杂性科学问题，包括纳米马达对NMA作用的强化，实现NMA结构与功能的优化设计。该项目将创制多功能Aβ解毒剂并发展相关理论，对AD药物开发具有重要指导意义。

Self-assembly of β-amyloid proteins (Aβ) produces fibrillar aggregates that are highly toxic to neuron cells, leading to the progressive neurodegeneration, i.e., Alzheimer’s disease (AD). Therefore, it is a great challenge to develop Aβ-targeted multifunctional antidotes for the prevention and treatment of AD. This proposal has put forward the idea of designing a near infrared (NIR) light-driven “nanomotor-based multifunctional antidote” (NMA). NMA will be fabricated by modifications of polymeric Janus nanoparticle (JNP) with entrapped black phosphorus quantum dots (BPQD) that not only have strong photothermal effect under NIR irradiation, but also are capable of chelating Cu2+ ions. The hydrophobic side of JNP is coupled with gold nanostars that have also strong photothermal effect under NIR irradiation, while the hydrophilic surface of JNP is modified with a peptide-based multifunctional inhibitor. The photothermal effect of gold nanostars on JNP produces a temperature gradient around the JNP, which drives the JNP to move in a microscopic scale, leading to the formation of an NIR light-driven nanomotor. The project is designed to systematically investigate the inhibitory effects of the surface inhibitor, intensification of the nanomotor on Aβ detoxification by NMA and the disaggregation of Aβ fibrils by the photothermal effect of entrapped BPQD. The studies will reveal the interplay of the photothermal effects of BPQD and the gold nanostars and the complex scientific issues about the effects of NMA on the conformational transition of Aβ, Aβ aggregation, and disaggregation of Aβ fibrils and the chelation of Cu2+ ions, particularly the intensification of the nanomotor on the NMA effects. The outcomes will help realize optimization of the NMA structure and function. The research will thus create a novel multifunctional agent against Aβ aggregation and neurotoxicity as well as develop related inhibitory theories. Therefore, it is of great significance for further development of neuroprotective agents for AD.