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CQ supporting nanometer gold blocking mesoporous silica controlled release system, preparation method and applications thereof

A technology of mesoporous silica and controlled release, which is applied in nervous system diseases, medical preparations of non-active ingredients, pharmaceutical formulas, etc., can solve undiscovered problems, achieve premature release, inhibit Aβ polypeptide aggregation, Effect of reducing apoptosis-inducing ability

Active Publication Date: 2015-11-11
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] So far, no reports have been found on nano-gold plugging mesoporous silica controlled release system while inhibiting the aggregation of Aβ polypeptide induced by metal ions and the spontaneous aggregation of Aβ polypeptide

Method used

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  • CQ supporting nanometer gold blocking mesoporous silica controlled release system, preparation method and applications thereof
  • CQ supporting nanometer gold blocking mesoporous silica controlled release system, preparation method and applications thereof
  • CQ supporting nanometer gold blocking mesoporous silica controlled release system, preparation method and applications thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1MSN-CQ-AuNPs

[0037]Preparation of MSN: Dissolve 0.1g of cetyltrimethylammonium bromide (CTAB) in 48mL of water and add 3.5mL of 0.2M NaOH. After the solution is heated to 85°C, stir vigorously for 1h; then, add 0.5mL of Tetraethyl silicate (TEOS), the mixed solution was stirred for 1 h; MSN was obtained by centrifugation, washed several times with ethanol and then centrifuged to remove ethanol; MSN was refluxed in HCl / methanol for 24 h to remove the surfactant CTAB; finally, centrifuged The MSNs were dried under vacuum at 60°C overnight to remove the solvent in the mesoporous pores.

[0038] MSN-NH 2 Preparation: 1.0g MSN was dissolved in 80.0mL anhydrous toluene and sonicated for 5min. Subsequently, 1.0 mL of 3-aminopropyltriethoxysilane (APTES) was added and refluxed for 24 h to modify 3-aminopropyltriethoxysilane onto the surface of MSN to obtain MSN-NH2.

[0039] Preparation of MSN-BA: 400 mg of purified MSN-NH 2 Dissolve in 20mL...

Embodiment 2

[0043] Example 2 Inhibitory effect of MSN-CQ-AuNPs on the spontaneous aggregation of Aβ and the aggregation of Aβ polypeptide induced by metal ions

[0044] The degree of aggregation of Aβ40 polypeptide into fibers was detected by dye ThT, and the fluorescence intensity of ThT was detected on a JASCOFP6500 fluorescence spectrophotometer. Aβ40 solution (30 μM) was incubated with 0.125, 0.25 and 0.5 mg / mL MSN or MSN-AuNPs at 37°C for 0 to 5 days. Aβ40 solution (30μM) with Cu 2+ (60 μM), 0.5 mg / mL MSN-CQ or MSN-CQ-AuNPs were incubated for 0 to 5 days. Take 50 μL from the incubation solution every day and incubate with 200 μL ThT (15 μM) for 15 min in the dark, and then detect the fluorescence intensity of ThT on a fluorescence spectrophotometer. ThT has an excitation wavelength of 440nm and an emission wavelength of 490nm. Experiments were repeated three times and standard deviations were calculated. Experimental results such as figure 2 As shown, MSN-CQ-AuNPs can inhibit t...

Embodiment 3

[0045] Example 3 Inhibitory effect of MSN-CQ-AuNPs on the spontaneous aggregation of Aβ and the neurotoxicity of Aβ polypeptide aggregation induced by metal ions

[0046] In this experiment, PC12 cells were purchased from ATCC Company, and the culture conditions were DMEM medium supplemented with 5% horse serum and 10% bovine serum, 5% CO 2 , at 37°C.

[0047] MTT test method: seed PC12 cells on a 96-well plate, 5×10 per well 3 Cells were cultured for 24 hours until the cells adhered to the wall. To detect the toxicity of Aβ40 fibrils, Aβ40 polypeptide (30 μM) was mixed with Cu 2+ (60 μM) and 0.5 mg / mL nanoparticles were incubated in cell culture medium at 37° C. for 3 days. Cells were then incubated in these incubation solutions for 72 h. To examine the toxicity of nanomaterials, the adherent PC12 (5×10 3 per well) were incubated with different concentrations of nanoparticles for 48 h. 60 μL / well of MTT solution was added 4 hours before the end of the culture. After 4 ...

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Abstract

The present invention relates to the field of metal nanometer material preparation, and specifically discloses a CQ supporting nanometer gold blocking mesoporous silica controlled release system, a preparation method and applications thereof. The preparation method comprises: S1, carrying out amination modification on mesoporous silica MSN to obtain MSN-NH2, and carrying out 4-carboxy phenyl boronic acid modification to obtain MSN-BA; S2, dissolving the MSN-BA in PBS, carrying out ultrasonic dispersion, adding CQ, carrying out a stirring reaction for 12-24 h, and washing to obtain CQ-supporting MSN-BA; and S3, dissolving the CQ-supporting MSN-BA in PBS, adding monosaccharide-modified AuNPs, carrying out a stirring reaction for 12-24 h, and washing to obtain MSN-CQ-AuNPs. According to the present invention, the MSN-CQ-AuNPs can inhibit the spontaneous aggregation of Abeta, further has the inhibition effect on the metal ion induced Abeta polypeptide aggregation, and can be adopted as the potential Alzheimer's disease treatment drug.

Description

technical field [0001] The invention relates to the field of preparation of metal nanomaterials, in particular to a CQ-loaded nano-gold plugging mesoporous silica controlled release system and its preparation method and application. Background technique [0002] Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory and cognitive dysfunction. AD is more common in the elderly, and the prevalence of AD in people over 60 years old is about 5-10%, while the prevalence of AD in people over 85 years old is as high as 40-50%. With the aging of the population and the lack of effective means of prediction and treatment, the number of AD patients has been increasing. The average survival period of AD patients is only 5.5 years, and the disease has become the fourth leading cause of death in the elderly after heart disease, cancer and stroke. However, acetylcholinesterase inhibitors and N-methyl-D-aspartic acid (NMDA), which have entered into clin...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K31/47A61K47/04A61K47/02A61P25/28
Inventor 刘杰杨丽聪周艳晖
Owner JINAN UNIVERSITY
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