Amyloid‐β Oligomer‐Targeted Gadolinium‐Based NIR/MR Dual‐Modal Theranostic Nanoprobe for Alzheimer's Disease

Abstract

While the deposition of amyloid-β (Aβ) plaques is one of the main pathological hallmarks of incurable Alzheimer's disease (AD), Aβ oligomers have been identified as a more appealing AD biomarker due to their being more pathogenic and neurotoxic. Therefore, the development of a sensitive and effective technique for oligomeric Aβ detection and imaging is beneficial for the early detection of AD, monitoring disease progression, and assessing the efficacy of potential AD drugs. Herein, the development and investigation of the first Aβ oligomer-specific Gd 3+ -based nanoparticles (NPs), NP@SiO 2 @F-SLOH as a multimodal near-infrared imaging (NIRI)/T 1weighted magnetic resonance imaging (MRI) contrast agent for real-time visualization of Aβ contents in an AD mouse model is reported. Remarkably, the NP@SiO 2 @F-SLOH is successfully applied for in vivo and ex vivo NIRI with high sensitivity and selectivity for Aβ oligomers and for MRI with good spatial resolution in different age groups in an AD mouse model. Furthermore, the NP probe exhibits a noticeable inhibitory effect on Aβ fibrillation and neuroprotection against Aβ-induced toxicity indicating its desirable therapeutic potential for AD. All these results illustrate the tremendous potential of this versatile and sensitive nanomaterial as an effective theranostic MRI nanoprobe for practical use.

Mesoporous Silica Nanoparticles in Bioimaging

“…This is exemplified in, for example, work by Qiao et al, where mesoporous silica-coated gadolinium-doped upconversion nanoparticles for MR/UCL have been reported for both dual-modal imaging and osteocyte-targeting therapy [ 170 ]. Another recent example by Wang et al where mesoporous silica-coated UCNPs additionally coated with a biomarker-selective fluorophore were used for both identification and therapy of Alzheimer’s disease ( Figure 14 ) [ 171 ].…”

“…UCL refers to upconversion luminescence. Reprinted with permission from reference [ 171 ]. Copyright (2020) Wiley-VCH.…”

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

“…The surface‐conjugated Aβo‐selective cyanine dye (F‐SLOH) enabled the nanoassembly to selectivity target Aβo, and the NIR fluorescence signal was significantly enhanced only when the F‐SLOH bound to Aβ. Therefore, this dual‐modal Aβo‐selective Gd 3+ ‐based nanoassembly can accurately indicate the existence of Aβo by NIRI and reveal its spatial distribution in AD mice of different ages by MRI (Figure 3a–d; C. Wang et al, 2020). Moreover, a DNAzyme‐powered 3D DNA walker structure composed of AuNPs, aptamer, Zn 2+ ‐dependent DNAzyme walking strands and TAMRA‐labeled hairpin substrate strands was also reported for revealing the level of Aβo in real‐time (Yin et al, 2020).…”

“…(e) Schematic illustration of Aβo sensitive assay and imaging based on target‐triggered DNAzyme‐driven 3D DNA walker fluorescence signal amplification technology; (f) confocal fluorescence images of BV‐2 cells incubated with 3D DNA walker nanoassembly, 3D DNA walker nanoassembly/Zn 2+ , 3D DNA walker nanoassembly/Aβo, and 3D DNA walker nanoassembly/Zn 2+ /Aβo. (g) in vivo fluorescence images and (h) relative fluorescence signal [F(t)/F(pre)] of the WT (top row) and Tg (bottom row) mice at selected time points before or after injection; (i) relative fluorescence signal [F(t)/F(pre)] of WT and Tg mice at 240 min after injection; (j) H&E staining of major organs of mice with/without 3D DNA walker nanoassembly injection Source : (a–d) Reprinted with permission from C. Wang et al (2020). Copyright 2020 Wiley; (c–d) reprinted with permission from Yin et al (2020).…”

Metals in Imaging of Alzheimer’s Disease

“…The MRI imaging allows nonradioactive diagnostics and is also cheaper and faster than PET imaging. The Gd 3+ PET imaging agents for Aβ visualization are also of interest [19].…”