Dual‐Modal NIR‐Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid‐β Species In Vivo

Abstract

Senile plaques, the extracellular deposit of amyloid-β (Aβ) 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-β (Aβ)-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 Aβ-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 Aβ species in vivo is reported. This Aβ-specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against Aβ-induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to Aβ 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.

Development of Non-Porous Silica Nanoparticles towards Cancer Photo-Theranostics

“…However, fluoresce imaging is not quantitative, and the image information is a surface-weighted in vivo system. Thus, multimodal imaging utilizing a combination of MRI and fluorescent imaging could facilitate the creation of a novel imaging system [ 141 , 142 , 143 ].…”

“…Hydrophobic iron oxide cores can be coated with silica shells using the reverse microemulsion method or siloxanes which contain hydrophobic parts, thus resulting in an MRI-detectable silica nanoparticle. Li et al reported Fe 3 O 4 @SiO 2 @SLCONHR nanoparticles by integrating highly Aβ-specific and turn-on fluorescence cyanine sensors for a neuroprotective dual-modal nanoprobe in vivo for both NIR imaging and MRI contrast [ 143 ]. Inorganic nanoparticles, such as Fe, are readily utilized as MRI biomedical imaging probes, due to their inherent T1- and T2-weighted contrasts.…”

Functional nanoassemblies for the diagnosis and therapy of Alzheimer's diseases

“…The NIRI was triggered only when the nanoassembly bound to Aβ due to the specificity of the fluorescence cyanine sensors for Aβ. Therefore, the colocalization of the NIRI and MRI signals provided a more accurate spatial distribution of Aβ in the AD brain (Y. Li, Xu, et al, 2018).…”

Cyanine Conjugate‐Based Biomedical Imaging Probes

“…Additionally, a hydrophilic silica layer was reported to improve the dispersity and stability of Fe 3 O 4 NPs as well. [99] Apart from the commonly used contrast agents, cyanine has been conjugated with manganese oxide (MnO) nanoparticles which remain in a relatively early stage. For example, Ye's lab modified MnO NPs with N-(Trimethoxysilylpropyl)ethylene diamine triacetic acid, trisodium salt to confer water dispersibility and stability; PEG-Cy5.5 was then conjugated on the surface (65) for dual-modal imaging of brain gliomas (Figure 12c).…”