Yu Dongqin, Zhang Haochen, Du Xiubo, Ren Jinsong, Qu Xiaogang
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun, Jilin, 130022, P. R. China.
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.
Small. 2025 Apr;21(13):e2410063. doi: 10.1002/smll.202410063. Epub 2025 Feb 24.
Oxidative stress is the crucial pathologic factor for causing neuron death and cognitive impairment in the progression of Alzheimer's disease (AD). As a special antioxidant, molecular hydrogen (H) is responsible for alleviating oxidative stress and associated inflammatory symptoms. However, in vivo continuous and efficient hydrogen accumulation is rather difficult to realize, thus frequent dosing is required to ensure the desired therapeutic effect. Herein, hydrogen-bonded organic frameworks (HOFs) composites are rationally designed to achieve sustainable near-infrared II (NIR-II) photocatalytic hydrogen evolution reaction for relieving neuroinflammation in AD model mice. The HOFs composites mainly consist of three parts: building block porphyrin as the photocatalyst, DSM (NIR-II-absorbing pyridinium hemicyanine dye) as fluorescent emitter, and platinum nanoparticles as co-catalyst. Under NIR-II laser illumination, DSM acts as an energy transducer to activate porphyrin to produce reductive hydrogen in situ. Specially, porphyrin selectively binds with the accumulated Cu ions in Aβ plaques and boosts H evolution. KLVFFAED (KD8) is covalently grafted on the HOFs to improve the blood-brain barrier permeability in vivo. This designed system exhibits an admirable therapeutic effect for relieving inflammation and recovering cognitive disorder in AD model mice, thus providing a new way for exploring HOFs used for sustainable hydrogen therapy.
氧化应激是阿尔茨海默病（AD）进展过程中导致神经元死亡和认知障碍的关键病理因素。作为一种特殊的抗氧化剂，分子氢（H₂）负责减轻氧化应激及相关炎症症状。然而，在体内持续高效地积累氢气相当困难，因此需要频繁给药以确保达到预期的治疗效果。在此，合理设计了氢键有机框架（HOFs）复合材料，以实现可持续的近红外二区（NIR-II）光催化析氢反应，从而缓解AD模型小鼠的神经炎症。HOFs复合材料主要由三部分组成：作为光催化剂的构筑单元卟啉、作为荧光发射体的DSM（吸收NIR-II的吡啶鎓半菁染料）以及作为助催化剂的铂纳米颗粒。在NIR-II激光照射下，DSM作为能量转换体激活卟啉原位产生还原性氢气。特别地，卟啉与Aβ斑块中积累的铜离子选择性结合并促进氢气生成。KLVFFAED（KD8）共价接枝在HOFs上以提高其体内血脑屏障通透性。该设计系统在缓解AD模型小鼠炎症和恢复认知障碍方面表现出令人满意的治疗效果，从而为探索用于可持续氢疗法的HOFs提供了一条新途径。
