Prof. Ricky Man Shing Wong (Department of Chemistry, Hong Kong Baptist University, SAR China) will give a lecture entitled “Multimodal Nanoprobe for Amyloid-β Targeted Imaging and ROS Sensing in Alzheimer’s Disease”.
Abstract:
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder featured by progressive and irreversible impairment of cognitive functions and memory loss due to progressive degeneration of synapses and neuronal loss. Oxidative stress caused by the overproduction of reactive oxygen species (ROS), which leads to oxidative damage and neuronal loss has been found to be an early event during AD pathogenesis. ROS overproduction has been shown to be closely associated with the presence of amyloid-β (Aβ) aggregates, the hallmark of AD. However, tools that can simultaneously detect and monitor the levels of oxidative stress and Aβ aggregates are rare, which are vital for early disease diagnosis, etiological investigations, and treatment assessment of the developed drugs.
Toward this end, we present herein our novel approach to develop a new class of a multimodal nanoprobe being capable of conducting Aβ-targeted NIR imaging, ratiometric responsive sensing of H2O2, and magnetic resonance (MR) imaging of Aβ aggregates in a single entity for more precise disease diagnosis and prognosis of AD. To integrate all these imaging functions together, a highly sensitive, Aβ-specific H2O2-responsive ratiometric NIR fluorescent probe that can apply for real time visualization of H2O2 level induced by Aβ ratiometrically in AD cell and mouse models was first developed. Meanwhile, paramagnetic NaGdF4 nanoparticles (NPs) were synthesized to acquire magnetic properties for MRI. The freshly synthesized NaGdF4 NPs were then protected by a mesoporous silica layer in which the developed H2O2-responsive probes were deposited onto the surface of the NPs leading to a H2O2-responsive NIR/MR multimodal imaging nanoprobe. This multimodal nanoprobe was shown to be able to target Aβ and visualize ratiometrically the endogenous H2O2 level in an AD cell model. Furthermore, this responsive nanoprobe was highly viable and sensitive to ratiometrically detect and monitor the Aβ-induced H2O2 level in APP/PS1 AD mouse model in real time with several age groups over time. Most importantly, this Aβ-targeted nanoprobe was shown to be an effective MRI contrast agent for in vivo T1-weighted MRI of Aβ content in an AD mouse model.
