Glyconanoparticle Aided Detection of β-Amyloid by Magnetic Resonance Imaging and Attenuation of β-Amyloid Induced Cytotoxicity

Abstract

The development of a noninvasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding treatment of the disease. The aggregates of β-amyloid are a pathological hallmark of Alzheimer's disease. Carbohydrates such as gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using superparamagnetic iron oxide glyconanoparticles to detect β-amyloid. The bindings of β-amyloid by the glyconanoparticles were demonstrated through several techniques including enzyme linked immunosorbent assay, gel electrophoresis, tyrosine fluorescence assay, and transmission electron microscopy. The superparamagnetic nature of the nanoparticles allowed easy detection of β-amyloid both in vitro and ex vivo by magnetic resonance imaging. Furthermore, the glyconanoparticles not only were nontoxic to SH-SY5Y neuroblastoma cells but also greatly reduced β-amyloid induced cytotoxicity to cells, highlighting the potential of these nanoparticles for detection and imaging of β-amyloid.

Heparin nanoparticles for β amyloid binding and mitigation of β amyloid associated cytotoxicity

“…4, 34 Shifting the equilibrium between the oligomers and fibril towards the more benign fibrils can potentially decrease the adverse effects of Aβ. 35–36 As Hep-SPION can reduce the proportions of Aβ oligomers (Figure 3A), we hypothesized that Hep-SPION could protect neuronal cells from Aβ induced toxicity.…”

“…36–37 Various concentrations of Aβ were incubated with SH-SY5Y cells in a 96-well cell culture plate. Cells in each well were collected and then mixed with 7-aminoactinomycin D (7-AAD), a fluorescent stain specific to dead cells.…”

Recent advances in biosensing using magnetic glyconanoparticles

“…Following this approach, Kouyoumdjian et a l . [36 ] reported the synthesis o f m agnetite glyconanoparticles functionalized with approximately 100 sialic acid copies per nanoparticle for the detection of β-amyloid aggregates by MRI. Similarly, amino-functionalized silica MNPs were modified with carboxylic groups and decorated with Lewis X (Le X ) and sialyl Le X (sLe X ) with use of the N-hydroxysuccinimide linker [37].…”

Glyconanomaterials: Emerging applications in biomedical research

“…Amino groups were subsequently introduced by treating the dextran layer with epichlorohydrin/NaOH followed by ammonia. The partially protected sialic acid derivative having a carboxylic acid end group was then conjugated to amine-MNPs by amide coupling, and the final glyco-MNPs were obtained after removing the protecting groups in aqueous NaOH [111]. Other examples, from our group, involved the preparation of PFPA-functionalized iron oxide nanoparticles by treating the particles with PFPA-phosphate.…”