Oxidative damage caused by upregulated nitric oxide (NO) plays an important role in the pathogenesis of Alzheimer’s disease (AD). Currently, stimulus-triggered theranostic agents have received much attention due to benefits on disease imaging and targeted therapeutic effects. However, the development of a theranostic agent triggered by NO for AD remains unexplored. Herein, through the mechanism analysis of the reaction between a fluorophore of 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) and NO, which we occasionally found and thereafter structure optimization of DPAC, a theranostic agent DPAC-(peg)₄-memantine was fabricated. In an AD cellular model, DPAC-(peg)₄-memantine exhibits NO sensing ability for AD imaging. Meanwhile, DPAC-(peg)₄-memantine shows improved therapeutic by targeted drug release triggered by NO and sustained therapeutic effects owing to the synergetic antioxidative abilities via the anti-AD drug and NO scavenging. This work provides an unprecedented avenue for the studies on not only AD but also other diseases with NO upregulation.

中文翻译：

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阿尔茨海默病细胞模型中内源性一氧化氮触发的治疗试剂的合理设计

由上调的一氧化氮（NO）引起的氧化损伤在阿尔茨海默病（AD）的发病机制中起重要作用。目前，刺激触发的治疗诊断药物因其对疾病成像的益处和靶向治疗效果而备受关注。然而，由 NO 引发的 AD 治疗诊断剂的开发仍未探索。在此，通过对 9,14-diphenyl-9,14-dihydrodibenzo[ a,c ]吩嗪 ( DPAC )的荧光团与 NO 反应的机理分析，我们偶然发现了这种反应，然后对治疗诊断剂DPAC进行了结构优化制造了DPAC- (peg) ₄ -美金刚。在 AD 细胞模型中，DPAC-(peg) ₄-美金刚对 AD 成像表现出 NO 传感能力。同时，DPAC- (peg) ₄ -美金刚通过由NO触发的靶向药物释放显示出改善的治疗效果，并且由于通过抗AD药物和NO清除的协同抗氧化能力而显示出持续的治疗效果。这项工作不仅为研究 AD 还为其他 NO 上调疾病的研究提供了前所未有的途径。