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Method for inhibiting aggregation of Abeta by using WS2 nanosheet and method for de-aggregating formed Abeta fiber aggregate

A technology of nanosheets and aggregates, applied in the field of medicine, can solve the problems of weak depolymerization ability, low blood-brain barrier permeability, and poor targeting.

Active Publication Date: 2015-06-17
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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  • Method for inhibiting aggregation of Abeta by using WS2 nanosheet and method for de-aggregating formed Abeta fiber aggregate
  • Method for inhibiting aggregation of Abeta by using WS2 nanosheet and method for de-aggregating formed Abeta fiber aggregate
  • Method for inhibiting aggregation of Abeta by using WS2 nanosheet and method for de-aggregating formed Abeta fiber aggregate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

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

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

[0048] Step 2: First, Aβ1-40 (product number U10012, purchased from American Peptide) was dissolved in hexafluoroisopropanol at a concentration of 1 mg / ml, the bottle was sealed, and shaken at 4°C for 2 hours to promote It was completely dissolved, and the stock solution was stored at -20°C. Befo...

Embodiment 2

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

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

[0056] Step 2: First, Aβ1-40 (product number U10012, purchased from American Peptide) was dissolved in hexafluoroisopropanol at a concentration of 1 mg / ml, the bottle was sealed, and shaken at 4°C for 2 hours to promote It was completely dissolved, and the stock soluti...

Embodiment 3

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

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

[0062] Figure 9For Example 3WS 2 The ThT fluorescence detection map of the inhibitory effect of nanosheets on Aβ1-40 aggregation, Figure 9 It can be seen that in CSF, WS 2 Nanosheets can still inhibit the fibrosis process of Aβ1-40 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 technical field of medicine, and in particular relates to a 2 Methods of nanosheets to inhibit A[beta] aggregation and methods to deaggregate formed A[beta] fibril aggregates. Background technique [0002] Alzheimer's disease (AD) is one of the most common forms of dementia. The clinical symptoms of AD patients mainly manifest as cognitive dysfunction, progressive memory loss, abnormal personality and so on. Its pathological features are the deposition of extracellular senile plaques 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 show that the excessive production and aggregation of Aβ is the key pathological event of AD. Inhibiting the aggregation behavior of Aβ and disaggregating the formed Aβ fiber aggregates is an effective way to prevent and treat AD. Substances that can regulate the aggreg...

Claims

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Application Information

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Patent Type & Authority Applications(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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