A Chiral Nanocomplex for Multitarget Therapy to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits

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‐NH₂@l‐MoS₂ 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 (H₂) production, and clear Aβ plaques. l‐MoS₂ 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‐MoS₂ QDs in scavenging reactive oxygen species at the lesion site via photocatalytic H₂ production. Loading l‐MoS₂ 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 H₂ 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.