Atomic-thick porous Pd nanosheets with antioxidant enzyme-like activities and photothermal properties for potential Alzheimer’s disease treatment

Nanostructure-based regulation on β-amyloid (Aβ) aggregation has shown potential in Alzheimer’s disease (AD) treatment. However, to develop an efficient therapeutic modality for Aβ-targeted AD therapy over nanostructures, with a deep understanding of mechanism at a molecular level, still remains a challenge. Herein, we report a multimodal modulation on Aβ aggregation by the subnanometer-thick and porous Pd nanosheets (NSs). The Pd NSs can not only effectively inhibit Aβ42 aggregation via a strong Pd-Aβ42 interaction, but display excellent antioxidant enzyme-like activities to eliminate the toxic reactive oxygen species (ROS) caused by the Aβ42 fibers, which restrains the ROS induced vicious cycle and slows down the development of AD. Besides, the Pd NSs exhibit robust near-infrared (NIR) photothermal effect, which enhances the depolymerization of Aβ42 fibers, while they are less cytotoxic and even promote cell growth. Moreover, the Pd NSs-based multimodal therapy can prolong the lifetime of nematodes and enhance their locomotion ability in in vivo tests. This work provides new insights into the development of ultrathin metallic nanostructures for AD therapy.