a ws 2 Method of inhibiting Aβ aggregation by nanosheets and method of deaggregating formed Aβ fiber aggregates

A technology of nanosheets and aggregates, applied in the field of medicine, can solve problems such as low blood-brain barrier permeability, high toxic and side effects, and weak depolymerization ability

Active Publication Date: 2017-11-17
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to their poor targeting, low blood-brain barrier (BBB) ​​permeability, and high toxicity and side effects, most inhibitors only show moderate inhibitory effect and weak depolymerization ability.

Method used

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  • a ws <sub>2</sub> Method of inhibiting Aβ aggregation by nanosheets and method of deaggregating formed Aβ fiber aggregates
  • a ws <sub>2</sub> Method of inhibiting Aβ aggregation by nanosheets and method of deaggregating formed Aβ fiber aggregates
  • a ws <sub>2</sub> Method of inhibiting Aβ aggregation by nanosheets and method of deaggregating formed Aβ fiber aggregates

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] WS 2 Nanosheets inhibit the self-aggregation of Aβ1-40:

[0047] Step 1: Prepare WS 2 Nanosheet: 100mg of WS in a nitrogen environment 2 The powder was dissolved in 1.6 M n-butyllithium solution and reacted. After 2 days, the mixture was filtered with Whatman#41 filter paper and washed with 100 mL of hexane 3 times. 300 mL of deionized water was added to the semi-dry precipitate obtained, and ultrasonic treatment 1 After hours, the solution was centrifuged, washed with deionized water 3 times to remove lithium ions and undispersed large particles, the supernatant was collected, and dialyzed with deionized water for 5 days to obtain WS 2 Nanosheets;

[0048] Step 2: First, dissolve Aβ1-40 (product number U10012, purchased from American Peptide) in hexafluoroisopropanol at a concentration of 1mg / ml, seal the bottle, and place it at 4℃ for 2 hours to shake It is completely dissolved and the stock solution is stored at -20°C. Before use, dry the hexafluoroisopropanol with a gent...

Embodiment 2

[0054] WS 2 Aβ1-40 fiber aggregates formed by photothermal depolymerization of nanosheets:

[0055] Step 1: Prepare WS 2 Nanosheet: 100mg of WS in a nitrogen environment 2 The powder was dissolved in 1.6 M n-butyllithium solution and reacted. After 2 days, the mixture was filtered with Whatman#41 filter paper and washed with 100 mL of hexane 3 times. 300 mL of deionized water was added to the semi-dry precipitate obtained, and ultrasonic treatment 1 After hours, the solution was centrifuged, washed with deionized water 3 times to remove lithium ions and undispersed large particles, the supernatant was collected, and dialyzed with deionized water for 5 days to obtain WS 2 Nanosheets;

[0056] Step 2: First, dissolve Aβ1-40 (product number U10012, purchased from American Peptide) in hexafluoroisopropanol at a concentration of 1mg / ml, seal the bottle, and place it at 4℃ for 2 hours to shake It is completely dissolved and the stock solution is stored at -20°C. Before use, dry the hexaf...

Embodiment 3

[0060] WS 2 Nanosheets inhibit Aβ1-40 aggregation in cerebrospinal fluid

[0061] The reaction conditions and steps are the same as those in Example 1, except that the treated Aβ1-40 and WS 2 The nanosheets are incubated in the cerebrospinal fluid.

[0062] Picture 9 Example 3WS 2 The ThT fluorescence detection chart of the inhibitory effect of nanosheets on the aggregation of Aβ1-40, Figure 9 shows that in the cerebrospinal fluid, WS 2 Nanoflakes can still inhibit the Aβ1-40 fibrosis process in a concentration-dependent manner.

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Abstract

The invention provides a method for inhibiting aggregation of Abeta by using a WS2 nanosheet and a method for de-aggregating formed Abeta fiber aggregate and belongs to the technical field of medicines. The method is used for inhibiting the aggregation of Abeta by utilizing a two-dimensional transition metal tungsten disulfide nanometer material; the WS2 nanosheet can be used for adsorbing an Abeta monomer by a Van Der Waals force between a planar base of the WS2 nanosheet and aromatic amino acids; meanwhile, the WS2 surface has negative charges and can be electrostatically combined with an Abeta positive ion group area to enhance the combination between the Abeta monomer and the WS2 sheet structure so as to inhibit the aggregation of the Abeta; the invention also provides a method for de-aggregating the formed Abeta fiber aggregate by using the WS2 nanosheet. The WS2 nanosheet has an obvious photo-thermal effect and can be used for photo-thermally de-aggregating the formed Abeta fiber aggregate under the illumination of near infrared light; meanwhile, the WS2 nanosheet has the effect of alleviating the cytotoxicity caused by Abeta.

Description

Technical field [0001] The invention belongs to the field of medical technology, and specifically relates to a WS 2 A method for nanosheets to inhibit Aβ aggregation and a method to depolymerize the formed Aβ fiber aggregates. Background technique [0002] Alzheimer's disease (AD) is one of the most common forms of dementia. The clinical symptoms of AD patients mainly include cognitive dysfunction, progressive memory loss, and personality abnormalities. Its pathological features are extracellular senile plaque deposition and intracellular neurofibrillary tangles in the brain. The main component of senile plaques is β-amyloid peptide (amyloidβ-peptide, Aβ). A large number of research results indicate that the overproduction and accumulation of Aβ are the key pathological events of AD. Inhibiting the aggregation behavior of Aβ and depolymerizing the formed Aβ fiber aggregates are effective ways to prevent and treat AD. Substances that can regulate the process of Aβ aggregation ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K33/24A61K9/00A61K41/00A61P25/28
Inventor 曲晓刚李蒙董凯李稳
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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