CN112826832B

CN112826832B - Nano reactor, preparation method and application thereof

Info

Publication number: CN112826832B
Application number: CN201911165856.3A
Authority: CN
Inventors: 刘健; 刘利红; 刘少敏; 田昊; 王昕尧; 张绍昆; 陈艳平; 吴宏
Original assignee: Dalian Institute of Chemical Physics of CAS
Current assignee: Dalian Institute of Chemical Physics of CAS
Priority date: 2019-11-25
Filing date: 2019-11-25
Publication date: 2022-05-17
Anticipated expiration: 2039-11-25
Also published as: CN112826832A

Abstract

The invention discloses a nano reactor, a preparation method and application thereof, wherein the nano reactor is a metal-loaded hollow silica nanoparticle; the metal comprises metal I and metal II; the metal I comprises any one of silver element, copper element, cobalt element, nickel element and magnesium element; the metal II is zinc element. The nanoparticles prepared by the preparation method have uniform size, high surface area, ordered mesopores and large pore volume. In addition, the nanoreactors are also ideal as antimicrobial agents for the treatment of MRSA infections.

Description

Nano reactor, preparation method and application thereof

Technical Field

The application relates to the technical field of inorganic nano-materials science, in particular to a nano-reactor, a preparation method and application thereof.

Background

Global antimicrobial drug resistance (AMR) leads to increased mortality and increased healthcare costs. In 2014, the World Health Organization (WHO) reported that the drug resistance rate of escherichia coli to cephalosporin exceeds 50% and the drug resistance rate of staphylococcus aureus to methicillin is 50% in 5 of 6 regions of the world health organization. To prevent the development of resistance, antibiotics must cope with a wide range of resistance mechanisms, such as enzymatic degradation, efflux and impermeability. One promising alternative to the current antibiotics are inorganic nanoparticles, which are capable of killing pathogens by various modes of action. First, the released metal ions can cause bacterial death; in addition to interfering with the metabolic system, heavy metal ions can induce fenton's reaction to generate Reactive Oxygen Species (ROS), thereby damaging DNA, proteins and cell membranes. On the other hand, nanoparticles provide additional physical and electrostatic interactions with the cell wall, leading to increased permeability of the cell membrane, and the probability of microbial gene mutations to escape these all-round mechanisms of action is zero.

Among the above antibacterial nanoparticles, in general, the nanoparticles having strong bactericidal activity are more toxic to host cells. Ag⁺The toxicity to epithelial cells was 4-12ppm, monocytes 1ppm and ocular epithelial cells 0.87 ppm. Thus, many strategies focus on minimizing toxicity through surface modification, controlled release and a combination of several antibacterial agents.

However, so far, it is about Ag based on nano-carrier⁺-Zn²⁺The studies on the co-delivery of antibacterial agents are rare, and basically, the silver-zinc composite nano materials, such as silver nanoparticles, are attached to the surface of zinc oxide, so that the controllable slow release of silver with high toxicity cannot be realized.

Disclosure of Invention

According to one aspect of the application, the nano reactor has the advantages of adjusting ion release time, being long-acting and safe, can reduce the toxic and side effects of heavy metal ions on bodies and improve the treatment effect, opens up a new and effective method for treating infection caused by drug-resistant bacteria, and brings a brand-new thought concept.

According to an aspect of the present application, there is provided a nanoreactor that is a metal-loaded hollow silica nanoparticle; the metal comprises a metal I and a metal II; the metal I comprises any one of silver element, copper element, cobalt element, nickel element and magnesium element; the metal II is zinc element.

Preferably, the metal I is silver.

Optionally, the particle size of the hollow silica nanoparticles is 50-1000 nm.

Optionally, the zinc element is present in the nanoreactor in the form of zinc oxide.

Optionally, the hollow silica nanoparticles include a framework and a hollow structure enclosed by the framework, the framework has a pore structure, zinc oxide is loaded on the framework, and silver is loaded in the hollow structure.

Optionally, the pore diameter of the pore structure in the framework is 1.2-50 nm.

Preferably, the pore structure in the framework is a micropore, and the aperture of the micropore is 1.2-2 nm; the pore diameter of the mesoporous structure in the framework is mesoporous, and the pore diameter of the mesoporous is 2-50 nm.

Optionally, the specific surface area of the hollow silica nanoparticles is 120-800 m²·g^-1。

Optionally, the content of the metal I in the nano reactor is 1-20 wt%; wherein the metal I is by weight of the metal itself.

Optionally, the content of zinc oxide in the nano reactor is 2-40 wt%.

Optionally, the content of the metal I in the nano reactor is 0.01-0.1 wt%; the content of the zinc oxide in the nano reactor is 0.1-2 wt%.

In another aspect of the present application, there is provided a method for preparing the above-mentioned nanoreactor, the method at least comprising the steps of:

a) reacting a mixture A containing a zeolite imidazole ester framework material, a metal I source and a reducing agent to obtain an intermediate product;

b) and carrying out hydrothermal reaction and calcination on a mixture B containing the intermediate product, the surfactant and the silicon dioxide precursor under an alkaline condition to obtain the nano-reactor.

Optionally, the zeolitic imidazolate framework material comprises at least one of zeolitic imidazolate framework-8, zeolitic imidazolate framework-67, zeolitic imidazolate framework-5.

Preferably, the zeolitic imidazolate framework material is zeolitic imidazolate framework-8.

Optionally, the reducing agent comprises at least one of sodium borohydride, sodium citrate, sodium hypophosphite, lithium aluminum hydride, and potassium borohydride.

Optionally, the surfactant comprises a cationic surfactant; the cationic surfactant comprises at least one of cetyl trimethyl ammonium bromide, octadecyl trimethyl ammonium chloride, dodecyl trimethyl ammonium bromide and dodecyl trimethyl ammonium chloride.

Optionally, the silica precursor comprises an organosilane; the organosilane comprises at least one of methyl orthosilicate, ethyl orthosilicate, vinyl trimethoxy silane, 3-aminopropyl triethoxy silane and mercaptopropyl trimethoxy silane.

Optionally, the hydrothermal reaction conditions are: the reaction temperature is 60-200 ℃; the reaction time is 1-48 h.

Optionally, the hydrothermal reaction conditions are: the reaction temperature is 60-150 ℃; the reaction time is 1-36 h.

Alternatively, the conditions of the calcination are: the reaction temperature is 300-1000 ℃; the reaction time is 2-10 h.

Alternatively, the conditions of the calcination are: the reaction temperature is 300-800 ℃; the reaction time is 3-10 h.

The obtaining of said mixture a in step a) comprises at least the following steps:

mixing a zeolite imidazolate framework material, a solution A containing metal I ions and a solution B containing a reducing agent to obtain the mixture A.

The obtaining of said mixture B in step B) comprises at least the following steps:

and mixing the intermediate product, the solution C containing the surfactant and the solution D containing the silicon dioxide precursor to obtain the mixture B.

Alternatively, in the step a), after the zeolite imidazolate framework material, the solution a and the solution B are mixed, the solution B is added under stirring, and the intermediate product is obtained after centrifugation, washing and drying.

Optionally, the solvent used for the washing is ethanol.

Optionally, the intermediate product is a metal I supported on a zeolitic imidazolate framework material.

Optionally, in the step b), after the intermediate product is added into the solution C, stirring is performed, the solution D is added, stirring is performed at room temperature, hydrothermal reaction is performed, centrifugation, drying, and calcination are performed, so as to obtain the nano-reactor.

Optionally, the stirring time is 1-24 hours.

Alternatively, the hydrothermal reaction is carried out in an autoclave.

Alternatively, the calcination is carried out under an air atmosphere.

Optionally, in the solution A, the molar volume ratio of the metal I ions to the solvent is 0.2-30 [ mu ] mol/mL.

Optionally, in the solution A, the molar volume ratio of the metal I ions to the solvent is 0.5-10 [ mu ] mol/mL.

Optionally, in the solution B, the mass-to-volume ratio of the reducing agent to the solvent is 2-40 mg/mL.

Optionally, in the solution B, the mass-to-volume ratio of the reducing agent to the solvent is 10-40 mg/mL.

Optionally, in the solution C, the mass-to-volume ratio of the surfactant to the solvent is 0.003-0.1 g/mL.

Optionally, in the solution C, the mass volume ratio of the surfactant to the solvent is 0.003-0.05 g/mL.

Optionally, in the solution D, the volume ratio of the silicon dioxide precursor to the solvent is 10-300 μ L/mL.

Optionally, in the solution D, the volume ratio of the silicon dioxide precursor to the solvent is 150-800 μ L/mL.

Optionally, the solution C further comprises ammonia water; in the solution C, the volume ratio of the ammonia water to the solvent is 6-400 mu L/mL.

Optionally, the content of ammonia water in the solution C is 6-50 μ L/mL of solvent.

Optionally, the solvent comprises at least one of methanol, ethanol, water.

Optionally, the solvent in solution C comprises water and ethanol; the volume ratio of the ethanol to the water is 0.4-10.

Alternatively, mesoporous zeolitic imidazolate framework-8 is prepared using techniques commonly used by those skilled in the art, such as: mixing the solution containing the organic ligand with a metal salt solution, standing at room temperature for 24h, centrifuging, washing and drying to obtain the mesoporous zeolite imidazole ester framework-8.

Alternatively, the microporous zeolitic imidazolate framework-8 is prepared by methods commonly used by those skilled in the art, such as: : and mixing the solution containing the organic ligand, the metal salt solution and the solution containing polyvinylpyrrolidone, standing at room temperature for 24 hours, centrifuging, washing and drying to obtain the microporous zeolite imidazole ester framework-8.

Optionally, the organic ligand comprises 2-methylimidazole.

Optionally, the metal salt solution comprises Zn (NO)₃)₂·6H₂Methanol solution of O.

Optionally, the molar ratio of the organic ligand to the metal salt is 1-8.

Optionally, the content of the polyvinylpyrrolidone in the solution containing polyvinylpyrrolidone is 0.016-1.5 g/mL of solvent.

Optionally, the content of the polyvinylpyrrolidone in the solution containing polyvinylpyrrolidone is 0.016-0.2 g/mL of solvent.

Optionally, the nano-reactor prepared from the mesoporous zeolite imidazolate framework-8 through the steps a) and b) is a hollow silica nano-particle with mesoporous walls loaded with metal I and zinc oxide.

Alternatively, the nanoreactor prepared from microporous zeolitic imidazolate framework-8 via steps a), b) is a hollow silica nanoparticle with microporous walls loaded with metal I and zinc oxide.

Alternatively, the purpose of the hydrothermal reaction step is to gradually dissolve the zeolitic imidazolate framework-8 to form zinc oxide, supported on hollow silica nanoparticles.

Alternatively, the purpose of the calcination is to remove the surfactant from the surface of the nanoreactor.

The application also provides an antibacterial drug, which comprises at least one of the nano-reactor and the nano-reactor prepared by the method.

The beneficial effects that this application can produce include:

1) the preparation technology of the nano reactor is simple, and the zeolite imidazole ester framework material plays a dual role in providing a hard template and zinc ions;

2) the nano reactor prepared by the method has the advantages that the adjustability of the controlled release can easily change the purposes of the pore diameter, the time for releasing active ingredients and the like by adjusting the proportion of the surfactant so as to meet the requirements of different treatment purposes;

3) when the long-acting application is carried out, the drug concentration of the drug administration part is far higher than the blood drug concentration, and the maintenance time is longer;

4) the nano reactor prepared by the method has high safety and low systemic toxicity.

Drawings

Fig. 1 is a transmission electron micrograph (a, b, c) and an elemental analysis (d) of the hollow silica nanoparticles having mesoporous walls on which silver and zinc oxide obtained in example 1 were supported.

Fig. 2 is a cumulative release curve of silver ions and zinc ions from silica nanoparticles with different pore wall structures.

Fig. 3 is representative photographs of the inhibition zones of various concentrations of a mesoporous nanoreactor C1 sample (a, B, C) and a microporous nanoreactor D1 sample (D, E, F) against methicillin-resistant staphylococcus aureus.

Detailed Description

The present application will be described in detail with reference to examples, but the present application is not limited to these examples.

The raw materials in the examples of the present application were all purchased commercially, unless otherwise specified.

The TEM test adopts a transmission electron microscope HT7700, and the elemental analysis test adopts a field emission high-resolution transmission electron microscope JEM-F200.

Example 1

Preparation of zeolitic imidazolate framework-8 (ZIF-8)1#

0.89g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 1.97g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperature and left to stand for 24 hours. The resulting white precipitate was collected by centrifugation, washed 3 times with methanol and finally dried in an oven at 60 ℃ overnight.

Preparation of intermediate A1

Sample # 1 was immersed in 10mL of a methanol solution containing 40. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 40mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample a1, intermediate a1 being a nanoparticle of metallic silver supported on ZIF-8.

Preparation of nano-reactor C1 (mesoporous)

0.1g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.2mL, 25 wt%) and stirred at room temperature (20 deg.C) then Ag was added&ZIF-8 nanoparticles. After stirring, 300. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 100 ℃ for 24 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 500 ℃ for 4 hours to achieve silver and zinc oxide loading in hollow silica with mesoporous walls, sample C1.

Preparation of the nanoreactor D1 (Millipore)

The preparation method of the nano-reactor D1 (micropore) is different from the preparation method of the nano-reactor C1 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 2, with the remaining steps being identical.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)2 #: first 0.89g Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol containing 0.5g of polyvinylpyrrolidone (PVP) to form a solution, and the rest of the procedure was the same as that for sample # 1.

Example 2

The zeolitic imidazolate framework-8 (ZIF-8) used in this example was sample # 1 prepared in example 1.

Preparation of intermediate A2

Sample No. 1 was immersed in 10mL of a methanol solution containing 20. mu. mol of metallic copper ions, and stirred well. Then 1mL of a methanol solution containing 10mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize intermediate A2.

Preparation of nano-reactor C2 (mesoporous)

0.1g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.2mL, 25 wt%) and stirred at room temperature before adding sample a 2. After stirring, 450. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 150 ℃ for 6 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 500 ℃ for 4 hours to achieve loading of Cu and zinc oxide in the hollow structured silica with mesoporous walls, sample C2.

Preparation of the nanoreactor D2 (Millipore)

The preparation method of the nano-reactor D2 (micropore) is different from the preparation method of the nano-reactor C2 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 2, with the remaining steps being identical.

Example 3

Preparation of intermediate A3

Sample # 1 was immersed in 10mL of a methanol solution containing 40. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 20mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize intermediate A3.

Preparation of nano-reactor C3 (mesoporous)

0.5g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.3mL, 25 wt%) and stirred at room temperature, then Ag was added&ZIF-8 nanoparticles. After stirring, 330. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 100 ℃ for 15 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 500 ℃ for 5 hours to achieve loading of Ag and zinc oxide in the hollow structured silica with mesoporous walls, i.e., sample C3. Preparation of the nanoreactor D3 (Millipore)

In the preparation of the nanoreactor D3 (micropore), the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 3, the remaining steps being identical.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)3 #: first 0.89g Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol containing 1.0g of polyvinylpyrrolidone (PVP) to form a solution, and the rest of the procedure was the same as that for sample # 1.

Example 4

Preparation of zeolitic imidazolate framework-8 (ZIF-8)4#

0.89g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 0.98g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperature without stirring for 24 hours. The resulting white precipitate was collected by centrifugation, washed 3 times with methanol and finally dried at 60 ℃ overnight.

Preparation of intermediate A4

Sample No. 4 was immersed in 10mL of a methanol solution containing 10. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 40mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample A4.

Preparation of nano-reactor C4 (mesoporous)

0.1g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.25mL, 25 wt%) and stirred at room temperature before adding sample a 4. After stirring, 300. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 100 ℃ for 12 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 300 ℃ for 10 hours to achieve silver and zinc oxide loading in hollow silica with mesoporous walls, sample C4.

Preparation of the nanoreactor D4 (Millipore)

The preparation method of the nano-reactor D4 (micropore) is different from the preparation method of the nano-reactor C4 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 3, with the remaining steps being identical.

Example 5

Preparation of Zeolite Imidazolate framework-8 (ZIF-8)5#

3.56g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 1.97g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperature without stirring for 24 hours. The resulting white precipitate was collected by centrifugation, washed 3 times with methanol and finally dried at 60 ℃ overnight.

Preparation of intermediate A5

Sample No. 5 was immersed in 10mL of a methanol solution containing 20. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 40mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample A5.

Preparation of nano-reactor C5 (mesoporous)

0.1g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (10 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.4mL, 25 wt%) and stirred at room temperature, then sample a5 was added. After stirring, 200. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 100 ℃ for 12 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 450 ℃ for 6 hours to achieve loading of Ag and zinc oxide in hollow silica with mesoporous walls, designated sample C5.

Preparation of the nanoreactor D5 (Millipore)

The preparation method of the nano-reactor D5 (micropore) is different from the preparation method of the nano-reactor C5 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 6, with the remaining steps being identical.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)6 #: first 3.56g Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol containing 2.0g of polyvinylpyrrolidone (PVP) to form a solution, and the rest was the same as sample # 1.

Example 6

Preparation of zeolitic imidazolate framework-8 (ZIF-8)7#

1.78g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 1.97g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperature without stirring for 24 hours. The resulting white precipitate was collected by centrifugation, washed 3 times with methanol and finally dried at 60 ℃ overnight。

Preparation of intermediate A6

Sample No. 7 was immersed in 10mL of a methanol solution containing 10. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 33mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample A6.

Preparation of nano-reactor C6 (mesoporous)

1.0g of cetyltrimethylammonium bromide was dissolved in a mixture of water (8mL) and ethanol (20 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.2mL, 25 wt%) and stirred at room temperature, then sample a6 was added. After stirring, 150. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 60 ℃ for 36 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 400 ℃ for 6 hours to achieve loading of Ag and zinc oxide in hollow silica with mesoporous walls, referred to as sample C6.

Preparation of the nanoreactor D6 (Millipore)

The preparation method of the nano-reactor D6 (micropore) is different from the preparation method of the nano-reactor C6 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 8, with the remaining steps being identical.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)8 #: first 1.78g Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol containing 1.0g of polyvinylpyrrolidone (PVP) to form a solution, and the rest was the same as sample # 1.

Example 7

Preparation of zeolitic imidazolate framework-8 (ZIF-8)9#

3.56g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 0.98g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperature without stirring for 24 hours. The resulting white precipitate was collected by centrifugation,washed 3 times with methanol and finally dried overnight at 60 ℃.

Preparation of intermediate A7

Sample No. 9 was immersed in 10mL of a methanol solution containing 20. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 12mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample A7.

Preparation of nano-reactor C7 (mesoporous)

0.2g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.8mL, 25 wt%) and stirred at room temperature, then Ag was added&ZIF-8 nanoparticles. After stirring, 600. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 24 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 100 ℃ for 12 hours. The solid product was recovered by centrifugation and dried at 60 ℃. The prepared solid product was calcined in a muffle furnace at 800 ℃ for 3 hours to achieve loading of Ag and zinc oxide in hollow silica with mesoporous walls, designated sample C7.

Preparation of the nanoreactor D7 (Millipore)

The preparation method of the nano-reactor D7 (micropore) is different from the preparation method of the nano-reactor C7 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 10, with the remaining steps being the same.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)10 #: first 3.56g Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol containing 0.8g of polyvinylpyrrolidone (PVP) to form a solution, and the rest was the same as sample # 1.

Example 8

Preparation of zeolitic imidazolate framework-8 (ZIF-8)11#

7.12g of Zn (NO)₃)₂·6H₂O was dissolved in 30mL of methanol to form a solution. 20mL of methanol containing 3.94g of 2-methylimidazole was poured into Zn (NO)₃)₂In solution. The mixture was kept at room temperatureWithout stirring for 24 hours. The resulting white precipitate was collected by centrifugation, washed 3 times with methanol and finally dried at 60 ℃ overnight.

Preparation of intermediate A8

Sample No. 11 was immersed in 10mL of a methanol solution containing 25. mu. mol of metallic silver ions, and stirred well. Then 1mL of a methanol solution containing 40mg of sodium borohydride was added to the mixture under vigorous stirring. After 30 minutes of reaction, the product was collected by centrifugation, washed several times with ethanol, and dried at 60 ℃ overnight to synthesize sample A8.

Preparation of nano-reactor C8 (mesoporous)

0.15g of cetyltrimethylammonium bromide was dissolved in a mixture of water (20mL) and ethanol (8 mL). Then, an aqueous ammonia solution (NH) was added₄OH, 0.2mL, 25 wt%) and stirred at room temperature, then Ag was added&ZIF-8 nanoparticles. After stirring, 400. mu.L of an ethyl orthosilicate solution was added to the suspension. The mixture was stirred at room temperature for 18 hours and subsequently heated under static conditions in a Teflon-lined autoclave at 120 ℃ for 6 hours. The solid product was recovered by centrifugation and dried at 60 ℃. Prepared nano-particle Ag&ZnO@SiO₂Calcination was carried out in a muffle furnace at 500 ℃ for 4 hours to achieve loading of Ag and zinc oxide in the hollow structured silica with mesoporous walls, sample C8.

Preparation of the nanoreactor D8 (Millipore)

The preparation method of the nano-reactor D8 (micropore) is different from the preparation method of the nano-reactor C8 (mesopore) in that: the zeolitic imidazolate framework-8 (ZIF-8) used was sample # 12, with the remaining steps being identical.

Preparation of zeolitic imidazolate framework-8 (ZIF-8)12 #: first, 7.12g of Zn (NO) is added₃)₂·6H₂O was dissolved in 30mL of methanol containing 3.5g of polyvinylpyrrolidone (PVP) to form a solution, and the rest was the same as sample # 1.

Example 9 nanoreactors C1-C8 (mesoporous) Structure characterization

The structure of the nanoreactors of samples C1-C8 was characterized by using a transmission electron microscope, which is typically shown in fig. 1, and corresponds to the TEM image and the elemental analysis of the sample C1 obtained in example 1, and it can be seen from the images that the hollow silica nanoparticle skeleton is a polyhedron structure, the shell layer has a very obvious mesoporous channel, and the elemental analysis shows that Zn, Si, and O are uniformly distributed on the skeleton, and Ag is uniformly dispersed in the hollow structure. .

Example 10 cumulative release of silver and zinc ions from silica nanoparticles of different pore wall structures

The cumulative release of silver and zinc ions from silica nanoparticles with different pore wall structures in the mesoporous nanoreactors of samples C1-C8 and the microporous nanoreactors of D1-D8 were tested, typically as shown in fig. 2, corresponding to the sample of example 1, and it can be seen that the mesoporous material released higher amounts of silver and zinc than the microporous material in 8 hours. In addition, mesoporous materials have a high initial burst followed by a slow and sustained release, which can be applied to achieve the need for immediate sterilization. The two materials release differently for up to 30 days.

Example 11 antimicrobial Property test

The antibacterial performance of the mesoporous nano-reactors C1-C8 and the microporous nano-reactors D1-D8 are tested. Typically, as shown in fig. 3, the test is performed corresponding to the sample in example 1, and fig. 3 is a representative photograph of the inhibition zones of various concentrations of the nanoreactor C1 (mesoporous) sample and the nanoreactor D1 (microporous) sample against methicillin-resistant staphylococcus aureus. As can be seen from the figure, the bacteriostatic performance of the mesoporous nanoreactor is more prominent than that of the microporous nanoreactor, and the difference is more obvious when the concentration of the nanoreactor is increased. The antimicrobial efficiency of the nanoreactors was determined using a Minimum Inhibitory Concentration (MIC) study against gram-positive methicillin-resistant staphylococcus aureus (MRSA). Corresponding to the sample in example 1, sample C1 delayed bacterial growth by 5 hours at 31.25ppm and completely inhibited growth by 24 hours at 125 ppm. Determination of Ag for MRSA⁺And Zn²⁺MIC of (a) was 3.2ppm and 40ppm, respectively.

From the above results, it is possible that the enhanced antibacterial performance of the mesoporous nanoreactor is attributed to the synergistic properties of Ag — Zn. By monitoring the concentration of ions released over timeIt was observed that Ag is supported in a hollow structured silica system with mesoporous walls⁺An initial burst of release followed by a slow, sustained release may suffice for immediate sterilization after application. In addition, Ag⁺The release of (a) gradually increases over the first 3 hours, with a maximum concentration of 2.3 ppm; interestingly, free [ Ag ] was found⁺]After this time, it decreased and reached 0.5ppm after 336 hours. Thus indicating an excess of Ag⁺Can be adsorbed on the nanocomposite surface and reduced to metallic Ag, which can ensure lower cytotoxicity.

Although the present application has been described with reference to a few embodiments, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the application as defined by the appended claims.

Claims

1. A nanoreactor, characterized in that the nanoreactor is a metal-loaded hollow silica nanoparticle;

the metal comprises a metal I and a metal II;

the metal I is silver element;

the metal II is zinc element;

the zinc element is present in the nanoreactor in the form of zinc oxide;

the content of the metal I in the nano reactor is 1-20 wt%;

wherein the metal I is by weight of the metal itself;

the content of the zinc oxide in the nano reactor is 2-40 wt%;

the hollow silica nanoparticle comprises a framework and a hollow structure formed by enclosing the framework, wherein the framework is provided with a pore structure, zinc oxide is loaded on the framework, and silver is loaded in the hollow structure.

2. The nanoreactor of claim 1, wherein the hollow silica nanoparticles have a particle size of 50 to 1000 nm.

3. The nanoreactor of claim 1, wherein the pore size of the mesoporous structure in the framework is from 1.2 to 50 nm.

4. The nanoreactor of claim 1,

the pore structure in the framework is a micropore, and the aperture of the micropore is 1.2-2 nm;

or the mesoporous structure of the framework is mesoporous, and the aperture of the mesoporous is 2-50 nm.

5. The nanoreactor of claim 1, wherein the hollow silica nanoparticles have a specific surface area of 120 to 800m²·g^-1。

6. Method for the preparation of a nanoreactor according to any of claims 1 to 5, characterized in that it comprises at least the following steps:

b) and carrying out hydrothermal reaction on the mixture B containing the intermediate product, the surfactant and the silicon dioxide precursor, and calcining to obtain the nano reactor.

7. The method of claim 6, wherein the zeolitic imidazolate framework material comprises at least one of zeolitic imidazolate framework-8, zeolitic imidazolate framework-67, zeolitic imidazolate framework-5.

8. The method of claim 6, wherein the reducing agent comprises at least one of sodium borohydride, sodium citrate, sodium hypophosphite, lithium aluminum hydride, and potassium borohydride.

9. The method of preparing a nanoreactor as in claim 6, wherein the surfactant comprises a cationic surfactant;

the cationic surfactant comprises at least one of cetyl trimethyl ammonium bromide, octadecyl trimethyl ammonium chloride, dodecyl trimethyl ammonium bromide and dodecyl trimethyl ammonium chloride.

10. The method of preparing a nanoreactor as in claim 6, wherein the silica precursor comprises an organosilane;

the organosilane comprises at least one of methyl orthosilicate, ethyl orthosilicate, vinyl trimethoxy silane, 3-aminopropyl triethoxy silane and mercaptopropyl trimethoxy silane.

11. The method for preparing a nanoreactor as claimed in claim 6, wherein the hydrothermal reaction is carried out under the following conditions:

the reaction temperature is 60-200 ℃; the reaction time is 1-48 h.

12. The method for preparing a nanoreactor as claimed in claim 6, wherein the calcination is carried out under the following conditions:

the reaction temperature is 300-1000 ℃; the reaction time is 2-10 h.

13. The method for preparing a nanoreactor according to claim 6, characterized in that the obtaining of the mixture A in step a) comprises at least the following steps:

14. The method for preparing a nano-reactor according to claim 13, wherein in the solution a, the molar volume ratio of the metal I ions to the solvent is 0.2 to 30 μmol/mL;

in the solution B, the mass-to-volume ratio of the reducing agent to the solvent is 2-40 mg/mL.

15. The method for preparing a nanoreactor as claimed in claim 6, characterized in that the obtaining of the mixture B in step B) comprises at least the following steps:

16. The method for preparing the nanoreactor according to claim 15, wherein in the solution C, the mass-to-volume ratio of the surfactant to the solvent is 0.003 to 0.1 g/mL;

in the solution D, the volume ratio of the silicon dioxide precursor to the solvent is 10-300 mu L/mL.

17. The method for preparing a nano-reactor according to claim 15, wherein the solution C further comprises ammonia;

in the solution C, the volume ratio of the ammonia water to the solvent is 6-400 mu L/mL.

18. An antibacterial drug comprising at least one of the nanoreactors of any one of claims 1 to 5, or the nanoreactors prepared by the method of any one of claims 6 to 17.