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Mesoporous silica nanoparticles modified by nucleic acid aptamer targeting polyethylene glycol and preparation method thereof

A mesoporous silica and nucleic acid aptamer technology, which is applied in the direction of pharmaceutical formulations, medical preparations of non-active ingredients, active ingredients of heterocyclic compounds, etc., can solve problems such as easy aggregation, precipitation, and large particle size, and achieve Good biocompatibility, improved water dispersibility and sustained release ability

Inactive Publication Date: 2018-12-21
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its large particle size, this type of transport carrier is easy to aggregate and precipitate in aqueous solution, thus limiting its application.

Method used

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  • Mesoporous silica nanoparticles modified by nucleic acid aptamer targeting polyethylene glycol and preparation method thereof
  • Mesoporous silica nanoparticles modified by nucleic acid aptamer targeting polyethylene glycol and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] 1. Preparation of mesoporous silica nanoparticles

[0030] 1. Dissolve 0.1 g of CTAB in 70 mL of water, 1 mL of ammonia water, and stir at room temperature for 15 minutes; the mass percent concentration of the ammonia water is 25%.

[0031] 2. Add 0.6 mL TEOS dropwise to the product of step 1 with vigorous stirring, and stir for 5 hours.

[0032] 3. Precipitate overnight at room temperature.

[0033] 4. Collect the precipitate by centrifugation and wash four times with ethanol.

[0034] 5. Vacuum dry at 100°C overnight, then calcined at 550°C for 6 hours to obtain mesoporous silica.

Embodiment 2

[0036] 2. Preparation of polyethylene glycol-modified mesoporous silica

[0037] 1. Add 100 mg mesoporous silica to 50 mL ethanol solution containing 25 uL APTES, stir at room temperature for 24 hours.

[0038] 2. Collect the precipitate by centrifugation and wash four times with ethanol.

[0039] 3. Vacuum drying at 80°C overnight to obtain mesoporous silica with surface-modified amine groups.

[0040] 4. The amine-modified mesoporous silica and amine-polyethylene glycol-carboxyl were reacted in PBS (pH 7.4) containing 10 mMEDC and 10 mM NHS in a molar ratio of 1:1 and stirred at room temperature for 2 to 4 hours.

[0041] In step 4 above, the amine groups of the amine-modified mesoporous silica need to be quantified, and the amine-modified mesoporous silica is dispersed in a 0.02 M sodium hydroxide solution and stirred for 60 hours. The supernatant (containing cleaved APTES) was taken to detect amine groups. The supernatant was mixed with PBS (0.2 M, pH 8), then 140 uL of...

Embodiment 3

[0043] 3. Preparation of PEG-modified mesoporous silica nanoparticles targeted by nucleic acid aptamers

[0044] 1. Centrifuge at 15,000 rpm for 10 minutes, and the precipitate is dispersed in PBS (pH 7.4) containing EDC and NHS. Add the terminal carboxyl-modified AS1411 nucleic acid aptamer and stir at room temperature for 24 hours.

[0045] 2. Centrifuge at 15,000 rpm for 10 minutes to obtain mesoporous silica-polyethylene glycol-nucleic acid aptamer nanoparticles.

[0046] 3. The obtained sample is analyzed by infrared spectroscopy and the nanometer particle size is measured.

[0047] figure 1 In order to react the amino-activated MSN with the carboxyl-activated PEG, MSN and PEG are generated through dehydration condensation, and the positions of the amide group or the external characteristic peaks are 3000cm-1 and 1689.0cm-1; so MSN-PEG (line b) and Compared with MSN (line a), the intensity of the peaks at the positions of 3000cm-1 and 1689.0cm-1 is obviously enhanced. ...

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Abstract

The invention discloses mesoporous silica nanoparticles modified by nucleic acid aptamer targeting polyethylene glycol and a preparation method thereof. The method comprises the following steps: synthesizing mesoporous silica through TEOS(tetraethyl orthosilicate), CTAB(cetyltrimethyl ammonium bromide), alkali and water; modifying amino on the surface of the mesoporous silica through APTES (aminopropyltriethoxysilane) in an ethanol solution; and connecting the primary amine end group of the mesoporous silica to the carboxyl group of polyethylene glycol by reacting, connecting the terminal carboxyl group of a nucleic acid aptamer to the amine group of the polyethylene glycol on the mesoporous silica by reacting, and carrying, by the mesoporous silica nanoparticles, a lipid-lowering drug such as atorvastatin. The mesoporous silica nanoparticles and the preparation method thereof have the characteristics that the nucleic acid aptamer is bound with the biological target with high affinityand high specificity, the polyethylene glycol can improve the water dispersion and the sustained release capability of the carrier, and the mesoporous silica can carry hydrophilic and hydrophobic drugs of different molecular weights due to the characteristics of unique mesoporous structure, huge specific surface area, easy surface modification and the like.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and relates to a mesoporous silica nanoparticle modified with nucleic acid aptamer targeting polyethylene glycol and a preparation method thereof. Background technique [0002] The formation of macrophage-derived foam cells is the main cytological change of atherosclerosis and can be used as a target for the diagnosis and treatment of atherosclerotic lesions. The formation of foam cells is due to the massive uptake of oxidized LDL, and scavenger receptors are responsible for 95% of the uptake of oxidized LDL. Nucleolin is a kind of scavenger receptor, and the nucleic acid aptamer AS1411 has a high degree of targeting to nucleolin. Therefore, it can target foam cells well by linking the AS1411 nucleic acid aptamer. [0003] Mesoporous silica is an ordered mesoporous nanomaterial, which has the advantages of regular nanopore structure, continuously adjustable pore size from 2 to 50 nm,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/26A61K47/10A61K47/04A61K31/40A61P9/10
CPCA61K9/5115A61K9/5123A61K9/5146A61K31/40A61P9/10
Inventor 魏坤莫灿龙牛雪明杨业国罗逍
Owner SOUTH CHINA UNIV OF TECH
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