Fluoro-substituted cyanine for reliable<i>in vivo</i>labelling of amyloid-β oligomers and neuroprotection against amyloid-β induced toxicity

Li, Yinhui; Xu, Di; Sun, Anyang; Ho, See‐Lok; Poon, Chung‐Yan; Chan, Hei‐Nga; Ng, Olivia; Yung, Kin Lam; Yan, Hui; Li, Hung‐Wing; Wong, Man Shing

doi:10.1039/c7sc03974c

Cited by 68 publications

(97 citation statements)

References 28 publications

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“…The selectivity of other oligomer-specific dyes has been rationalized through docking studies with the X-ray crystallographic structures of triangular trimers reported by our laboratory. 22–24 BODIPY-based probes, 22 developed by the Chang group, spiropyran-based probes, 23 developed by the Yi group, and cyanine-based probes, 24 developed by the Wong group, all specifically stain Aβ oligomers. To explain the oligomer-specific reactivity of these probes, all three groups performed docking simulations, in which the probes were docked on a triangular trimer formed by an Aβ-derived peptide (PDB 4NTR).…”

Section: Resultsmentioning

confidence: 99%

Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Aβ

et al. 2018

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Soluble oligomers of the β-amyloid peptide, Aβ, are associated with the progression of Alzheimer's disease. Although many small molecules bind to these assemblies, the details of how these molecules interact with Aβ oligomers remain unknown. This paper reports that crystal violet, and other C3 symmetric triphenylmethane dyes, bind to C3 symmetric trimers derived from Aβ. Binding changes the color of the dyes from purple to blue, and causes them to fluoresce red when irradiated with green light. Job plot and analytical ultracentrifugation experiments reveal that two trimers complex with one dye molecule. Studies with several triphenylmethane dyes reveal that three N, N-dialkylamino substituents are required for complexation. Several mutant trimers, in which Phe, Phe, and Ile were mutated to cyclohexylalanine, valine, and cyclohexylglycine, were prepared to probe the triphenylmethane dye binding site. Size exclusion chromatography, SDS-PAGE, and X-ray crystallographic studies demonstrate that these mutations do not impact the structure or assembly of the triangular trimer. Fluorescence spectroscopy and analytical ultracentrifugation experiments reveal that the dye packs against an aromatic surface formed by the Phe side chains and is clasped by the Ile side chains. Docking and molecular modeling provide a working model of the complex in which the triphenylmethane dye is sandwiched between two triangular trimers. Collectively, these findings demonstrate that the X-ray crystallographic structures of triangular trimers derived from Aβ can be used to guide the discovery of ligands that bind to soluble oligomers derived from Aβ.

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Section: Resultsmentioning

confidence: 99%

Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Aβ

et al. 2018

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“…It has been reported that inorganic filler such as rattan powder, glass fiber, etc. increases the tensile modulus of polymeric composites, yet causing the decrease of the strength and toughness . This could be attributed to the stress concentration or poor fiber‐matrix adhesion.…”

Section: Introductionmentioning

confidence: 99%

Interfacial strengthening of polypropylene composites via bimodal porosity in Rice husk ash: Comparison with calcium carbonate reinforcement

Sharma

Lohia²,

Sharma³

et al. 2018

J of Applied Polymer Sci

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Polypropylene is used in the textile industry in the manufacturing of plastic yarns, tapes, etc., but its low tensile strength and Young's modulus limits its associated applications. Composites of polypropylene with reinforcement of CaCO3 and rice husk ash were processed by compression molding. Bimodal porosity in rice husk ash particles has shown an improved interfacial anchoring effect via capillary effect resulting in enhanced mechanical properties, whereas such an effect is not observed with CaCO3 reinforcement in polypropylene matrix. On reinforcement with 10 wt % of each of rice husk ash and CaCO3, thermal decomposition temperature of polypropylene (333.3 °C) shifted to higher value of 415.9 °C and polypropylene Young's modulus (749.5 MPa) increased to 789.5 MPa (by 5.3%), but tensile strength decreased from 23.5 to 21.2 MPa (by 2.3 MPa only). The isolated contribution of CaCO3 and rice husk ash has been delineated, and resulting interfacial strengths have been quantified using analytical models. Rice husk ash has shown a stronger interfacial anchoring and can effectively replace CaCO3 as reinforcement for achieving improved mechanical and thermal properties of polypropylene composites. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 46989.

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“…As part of our effort on developing versatile probes for Aβ species imaging in vivo, we report herein a novel nontoxic and blood brain barrier (BBB) permeable NIR/MR dual‐modal imaging probe based on Aβ‐targeting carbazole‐based cyanine NIR fluorophores chemically conjugated onto superparamagnetic iron oxide nanoparticles (Fe 3 O 4 NPs) affording NIR/MR active Fe 3 O 4 @SiO 2 @SLCONHR NPs. Strong binding interactions between Aβ species and cyanine fluorophore have given rise to a large fluorescence enhancement in NIR region and MR signal.…”

Section: Methodsmentioning

confidence: 99%

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

Chan

et al. 2018

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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.

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Fluoro-substituted cyanine for reliablein vivolabelling of amyloid-β oligomers and neuroprotection against amyloid-β induced toxicity

Abstract: A fluoro-substituted cyanine showing reliable in vivo labelling of Aβ oligomers and potent neuroprotective effect against Aβ-induced toxicities is reported as a novel theranostic agent for the early diagnosis and therapy of Alzheimer's disease.

Cited by 68 publications

References 28 publications

Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Aβ

Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Aβ

Interfacial strengthening of polypropylene composites via bimodal porosity in Rice husk ash: Comparison with calcium carbonate reinforcement

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

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