Aβ-targeted NIRI/dual-mode T1- and T2-weighted MRI multimodal theranostic nanoprobe for early diagnosis of Alzheimer's disease

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The lack of amyloid (Aβ)-targetability and poor blood-brain barrier (BBB) penetrability of existing contrast agents cannot enable magnetic resonance (MR) imaging to visualize Aβ plaques for diagnosis and prognosis of Alzheimer's disease (AD). We present herein an advanced multimodal theranostic nanoprobe that can bind Aβ aggregates, conduct NIR fluorescence imaging, perform dual-mode T 1 - and T 2 -weighted MR imaging as well as inhibit Aβ self-aggregation and exhibit neuroprotection against Aβ-induced toxicity for in vivo real-time detection and visualization of Aβ plaques for precise diagnosis of AD. The nanoprobe was designed and developed from silica-enclosed superparamagnetic iron oxide nanoparticles that were surface-functionalized with cyanine fluorophore conjugated gadolinium(III) complex molecular dyads. This versatile nanoprobe showing excellent Aβ selectivity and targetability as well as BBB permeability, was highly effective for in vivo and ex vivo NIR fluorescence imaging of Aβ aggregates in various age groups of AD mouse model, Furthermore, the greatly enhanced longitudinal relaxivity ( r 1 = 43.68 mM −1 s −1 ) and large transverse relaxivity ( r 2 = 110.89 mM −1 s −1 ) enabled the nanoprobe for highly sensitive real time in vivo and ex vivo dual-mode T 1 - and T 2 -weighted MR imaging of Aβ aggregates in various age groups of AD mice enabling the differentiation from the normal counterparts.