Dual-Modal NIR-Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid-beta Species In Vivo

Senile plaques, the extracellular deposit of amyloid-beta (A beta) peptides, are one of the neuropathological hallmarks found in Alzheimer's disease (AD) brain. The current method of brain imaging of amyloid plaques based on positron emission tomography (PET) is expensive and invasive with low spatial resolution. Thus, the development of sensitive and nonradiative amyloid-beta (A beta)-specific contrast agents is highly important and beneficial to achieve early AD detection, monitor the disease progression, and evaluate the effectiveness of potential AD drugs. Here a neuroprotective dual-modal nanoprobe developed by integrating highly A beta-specific and turn-on fluorescence cyanine sensors with superparamagnetic iron oxide nanoparticles as an effective near-infrared imaging (NIRI)/magnetic resonance imaging (MRI) contrast agent for imaging of A beta species in vivo is reported. This A beta-specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against A beta-induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to A beta species, and MRI with high spatial resolution in an APP/PS1 transgenic mice model. Its potential as a powerful in vivo dual-modal imaging tool for early detection and diagnosis of AD in humans is affirmed.