Neural stem cells (NSC) transplantation is garnering considerable attention in the treatment of neurodegenerative diseases that are associated with cognitive decline. Current methods are mainly based on neuron-directional differentiation and NSC niche components majorization to promote neurogenesis. Unfortunately, the pathologically high level of oxidative stress will damage the neurons derived from NSC during therapy, compromising the neurogenesis effect. Herein, a facile and effective strategy has been presented for modulation of neuron-directional differentiation and amelioration of oxidative stress by integrating antioxidative nanozymes (ceria) into metal-organic frameworks (MOF) for synergistically enhancing neurogenesis. Specially, small interfering RNA (siSOX9) and retinoic acid (RA) are loaded in the MOF. The H₂O₂-responsive MOF would release cargos in the lesion area to promote neuron-directional differentiation. Moreover, the integrated ceria can perform robust SOD and CAT mimetic activities, which are capable of eliminating ROS and circumventing its oxidative damage to newborn neurons, leading to the longer survival rate and more enhanced outgrowth of the newborn neurons. With the gratifying drug delivery efficiency of MOF and excellent antioxidative capacity of nanozymes, the rational-designed nanoparticles can considerably promote neurogenesis and improve the cognitive function of aged 3 × Tg-AD (triple transgenic AD mouse model) mice. Our work provides a new way to promote nerve regeneration with the help of nanozymes.

神经干细胞（NSC）移植在与认知能力下降相关的神经退行性疾病的治疗中引起了广泛的关注。当前的方法主要基于神经元定向分化和NSC利基成分的广泛化，以促进神经发生。不幸的是，病理上高水平的氧化应激会在治疗过程中损害源自NSC的神经元，损害神经发生作用。本文中，已经提出了一种通过将抗氧化纳米酶（二氧化铈）整合到金属有机骨架（MOF）中以协同增强神经发生的方式来调节神经元定向分化和减轻氧化应激的简便有效的策略。特别是，将小的干扰RNA（siSOX9）和视黄酸（RA）装入MOF。H ₂O ₂响应型MOF将在病变区域释放货物以促进神经元方向的分化。此外，整合的二氧化铈可以执行强大的SOD和CAT模拟活动，能够消除ROS并避免其对新生神经元的氧化损伤，从而导致更长的存活率和新生神经元的长出。凭借令人满意的MOF药物递送效率和出色的纳米酶抗氧化能力，合理设计的纳米颗粒可以显着促进3×Tg-AD（三重转基因AD小鼠模型）小鼠的神经发生并改善其认知功能。我们的工作提供了一种借助纳米酶促进神经再生的新方法。