A Chiral Nanocomplex for Multitarget Therapy to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits
Huarong Tan, Yuqi Huang, Shuqing Dong, Zetai Bai, Cheng Chen, Xiunan Wu, Minghao Chao, Hanrong Yan, Shaoshen Wang, Deqin Geng, Fenglei Gao
Abstract
Abstract Alzheimer's disease (AD) is a severe neurodegenerative condition characterized by inflammation, beta‐amyloid (Aβ) plaques, and neurodegeneration, which currently lack effective treatments. Chiral nanomaterials have emerged as a promising option for treating neurodegenerative disorders due to their high biocompatibility, strong sustained release ability, and specific enantiomer selectivity. The development of a stimulus‐responsive chiral nanomaterial, UiO‐66‐NH 2 @ l ‐MoS 2 QDs@PA‐Ni (MSP‐U), for the treatment of AD is reported. MSP‐U is found to stimulate neural stem cell (NSCs) differentiation, promote in situ hydrogen (H 2 ) production, and clear Aβ plaques. l ‐MoS 2 QDs modified with l ‐Cysteine ( l ‐Cys) effectively enhance the differentiation of NSCs into neurons through circularly polarized near‐infrared radiation. Doped‐phytic acid nickel (PA‐Ni) improves the activity of l ‐MoS 2 QDs in scavenging reactive oxygen species at the lesion site via photocatalytic H 2 production. Loading l ‐MoS 2 QDs with UiO‐66 type metal oxide suppresses electron–hole recombination effect, thereby achieving rapid charge separation and improving transport of photogenerated electrons, leading to significantly improved H 2 production efficiency. The photothermal effect of MSP‐U also clears the generated Aβ plaques. In vivo evaluations show that MSP‐U improves spatial cognition and memory, suggesting a promising potential candidate for the treatment of AD using chiral nanomaterials.