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

Abstract

AbstractAlzheimer'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.