Work

Precise Aβ clearance and antioxidant therapy in Alzheimer’s disease via photoacoustic imaging-guided palladium hydride nanosheet-mediated photothermal treatment

Year: 2026

Type: article

Abstract: Inflammation and oxidative stress are critical pathological hallmarks of Alzheimer’s disease (AD). Hydrogen therapy shows promise due to its selective hydroxyl radical (∙OH) scavenging capacity, yet conventional hydrogen delivery fails to effectively accumulate in the brain due to low solubility and rapid diffusion. Here, we report ultra-small palladium hydride (PdH) nanosheets as a dual-functional nanomedicine for AD treatment. The PdH nanosheets exhibit high hydrogen-releasing efficiency via autocatalysis, enabling in situ ∙OH scavenging in the brain. Concurrently, their near-infrared (NIR) photothermal effect, degrading amyloid-β (Aβ) aggregates and transiently enhancing blood-brain barrier (BBB) permeability for improved drug delivery. In AD mice, intravenous PdH treatment combined with NIR irradiation significantly reduced escape latency in the Morris water maze, paralleling reductions in brain Aβ plaques and ROS levels. This study establishes a synergistic strategy of nanoscale hydrogen delivery and photothermal therapy, addressing the dual challenges of BBB penetration and multi-pathology intervention in AD. Not applicable. Innovative application of nanomaterials We innovatively use ultra - small palladium hydride (PdH) nanosheets as a dual - functional nanomedicine for Alzheimer’s disease (AD) therapy. Their self - catalyzed efficient hydrogen release enables in - situ・OH scavenging in the brain, which cannot be easily achieved by traditional hydrogen therapy due to hydrogen’s low solubility and fast diffusion in brain inflammatory sites. Synergy of photothermal and hydrogen therapy The near - infrared (NIR) photothermal effect of PdH nanosheets can degrade amyloid - beta (Aβ) aggregates while transiently enhancing blood - brain barrier (BBB) permeability to improve drug delivery efficiency. This synergistic strategy of combining photothermal and hydrogen therapy offers a new approach for AD treatment, addressing multiple pathological features like Aβ aggregation, oxidative stress, and neuroinflammation. Precise imaging - guided treatment Photoacoustic imaging is utilized to monitor and guide the treatment process in real - time, enabling precise therapy. With NIR - II FL imaging technology, PdH nanosheets’ accumulation in the brain and stable use can be accurately observed, allowing for precise localization of AD lesions and treatment - outcome assessment, thus enhancing the treatment’s accuracy. Efficient Aβ clearance and antioxidant therapy Under NIR irradiation, PdH nanosheets can markedly reduce Aβ plaques and reactive oxygen species (ROS) levels in AD mice brains, shorten escape latency, and improve cognitive deficits. This provides robust evidence for AD treatment. Problem or Issue Alzheimer’s disease (AD), a prevalent neurodegenerative disorder, is marked by amyloid-beta (Aβ) accumulation, reactive oxygen species (ROS) production, and neuroinflammation. With the global population aging, the incidence of AD is rising yearly, projected to surpass 150 million dementia cases worldwide by 2050. AD poses a significant threat to global health and social care. However, no effective drug to reverse AD has been found yet due to its complex and unclear pathogenesis and long onset time. What is Already Known Hydrogen therapy shows promise due to its selective scavenging capacity of hydroxyl radicals (∙OH). But conventional hydrogen delivery methods fail to effectively accumulate hydrogen in the brain because of low solubility and rapid diffusion. Many therapeutic drugs for AD, such as peptides, organic molecules, and metal/supramolecular complexes, have been designed and synthesized, but they have average inhibitory efficiency and limited dissociation ability. What this Paper Adds This study reports ultra-small palladium hydride (PdH) nanosheets as a dual-functional nanomedicine for AD treatment. PdH nanosheets can release hydrogen efficiently through autocatalysis, enabling in situ ∙OH scavenging in the brain. Meanwhile, their near-infrared (NIR) photothermal effect can degrade Aβ aggregates and transiently enhance blood-brain barrier (BBB) permeability for improved drug delivery. In AD mice, intravenous PdH treatment combined with NIR irradiation significantly reduced escape latency in the Morris water maze, along with reductions in brain Aβ plaques and ROS levels. This study establishes a synergistic strategy of nanoscale hydrogen delivery and photothermal therapy, addressing the dual challenges of BBB penetration and multi-pathology intervention in AD. Who would benefit from the new knowledge in this paper The findings of this research will benefit patients with AD and their medical care teams. By offering a novel therapeutic strategy, it is expected to enhance the cognitive function, learning ability, and memory of AD patients. This provides new insights and experimental evidence for the development of more effective treatment methods for AD and also offers valuable reference for researchers in the field of nanomedicine, promoting the application of nanotechnology in the treatment of neurodegenerative diseases.

Source: BMC Neuroscience

DOI: 10.1186/s12868-025-00994-0