Two-Photon Excited Near-Infrared Emissive Multifunctional Gold Nanoclusters for Imaging and Photothermal Treatment for Alzheimer's Disease

Neurodegenerative diseases are a global epidemic with significant health, social and economic implications and despite intensive research, there is still no cure for them. Alzheimers disease (AD) is the most prevalent neurological disorder having symptoms of the progressive memory loss, neuronal cell death, loss of immune response and cognitive function, eventually leading to patient death. Amyloid- (A) protein is the main neuropathic agent in AD and aggregation of A plaques are found in the brain tissue of patients suffering from this disease. The application of nanomaterials has emerged as a new frontier in nanomedicine for the treatment of AD. Among various nanomaterials, ultrasmall gold nanoclusters (Au NCs) may serve as a promising choice for the diagnosis and treatment of AD from the very early stage which can be well justified by the advantages of Au NCs in terms of their diverse physicochemical properties, biocompatibility and biodistribution, high surface to volume ratio, ease for functionalisation and drug loading, bloodbrain barrier (BBB) translocation and the possibility of two-photon excitation. The main objective of our research is to advance in the development of new, biocompatible multifunctional nanomaterials for the detection of amyloids with high spatial resolution and the subsequent degradation of amyloid aggregates using a non-invasive approach. In this regard, the blinking and non-linear optical properties of the Au NCs enable its potential for nanoscopic imaging of amyloid and two-photon photothermal ablation of amyloid aggregates. Another advantage of the proposed multifunctional nanomaterials is that they can also be used as drug delivery vehicles to penetrate the cell membrane and BBB to deliver anti-amyloid drugs that exhibit effective imaging-guided photothermal efficacy. This research will use state-of-the-art technology to develop a multifunctional phototheranostic nanomedicine for the detection and treatment of amyloid diseases.