Multifunctional nanoprobe for near-infrared and magnetic resonance dual-modal amyloid-β imaging and oxidative stress monitoring in early stage of Alzheimer's disease

Oxidative stress, closely linked to the presence of amyloid-β (Aβ) aggregates and leading to oxidative damage, and neuronal loss, is an early event during Alzheimer's disease (AD) pathogenesis. Tools that can monitor the levels of oxidative stress and Aβ content are imperative for improved diagnosis and disease progression, mechanistic studies of etiology, and evaluation of treatment effectiveness for this incurable disease. A multimodal H2O2-responsive fluorescent probe surface-coated Gd3+-based nanoprobe capable of Aβ targeting and NIR imaging, selective/ratiometric sensing of endogenous H2O2 induced by Aβ, and magnetic resonance (MR) imaging of Aβ aggregates for AD is firstly developed. Besides sensing the endogenous H2O2 level in an AD cell model, this nanoprobe can effectively target Aβ plaques and specifically detect and monitor the Aβ-induced H2O2 level ratiometrically in vivo in different ages of APP/PS1 transgenic mice over time. Remarkably, this Aβ-targeted nanoprobe can also serve as a highly effective and sensitive MRI contrast agent to detect and differentiate the Aβ content in different ages of AD mice. Our findings demonstrate that this ROS-responsive multimodal nanoprobe design strategy opens up a new avenue to develop an advanced class of multimodal probe for complementary investigations of cerebral Aβ by multiple imaging techniques.