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.