Water-soluble metal oxide quantum dot as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of nano antibacterial materials, and particularly relates to a water-soluble metal oxide quantum dot as well as a preparation method and application thereof. The preparation method of the water-soluble metal oxide quantum dots comprises the following steps: mixing a metal salt, a lower alcohol solvent and a hydrophilic surfactant to obtain a metal salt mixed solution; the metal salt comprises one or more of zinc salt, silver salt and copper salt; adding an alkaline alcohol solution into the metal salt mixed solution, continuously stirring, and carrying out solid-liquid separation to obtain the water-soluble metal oxide quantum dots; the continuous stirring time is 20 to 80 minutes. The metal oxide quantum dot nano material prepared by the invention can generate ROS (reactive oxygen species), has a bacteriostatic effect, has a good bactericidal effect on gram-positive bacteria and gram-negative bacteria, and does not induce drug resistance.

Description

Technical Field

[0001] The invention belongs to the technical field of nano antibacterial materials, and specifically relates to a water-soluble metal oxide quantum dot and a preparation method and application thereof. Background Art

[0002] The widespread use of antibiotics has led to the emergence of a large number of drug-resistant bacteria, resulting in the failure of many antibiotic treatments. Infections caused by drug-resistant bacteria have brought great harm to human health. The speed of drug research and development cannot keep up with the development of bacterial resistance. The emergence of drug-resistant bacteria may result in a lack of drugs available. Therefore, it is of great significance to find a material that is effective against both sensitive and resistant bacteria.

[0003] Metal ions have great potential for application in the treatment of bacteria. For example, silver ions, copper ions, zinc ions, etc. can all be made into products with antibacterial properties. Compared with organic antimicrobial agents, inorganic antimicrobial agents have the characteristics of high sterilization rate, good safety, long-term effect, no drug resistance, etc. for viruses, bacteria and fungi. They have good heat stability and broad application prospects. They have been valued by various countries and have gradually been widely used. However, excessive metal ions can be toxic to the body.

[0004] Metal oxide quantum dots are an emerging nanomaterial with a particle size between 1 and 10 nm. Metal oxide quantum dots can produce ROS and have bactericidal and antibacterial effects. Zinc oxide quantum dots (ZnO QDs) are the most widely studied antibacterial material because of their low price, abundant sources and good antibacterial effect. The synthesis methods of zinc oxide quantum dots include hydrothermal method, vapor precipitation method and sol-gel method. Among them, the sol-gel method has low cost, high reliability, good repeatability, simple process, and easy control of the physical properties and morphology of nanoparticles. Chinese patent CN 112830510A discloses a method for synthesizing zinc oxide quantum dots, using sodium methoxide as an alkali source, and using the sol-gel method to synthesize zinc oxide quantum dots in large quantities, but the antibacterial effect of the zinc oxide quantum dots obtained is not good, and a higher concentration is required to play a bactericidal role. Summary of the invention

[0005] In view of this, the purpose of the present invention is to provide a water-soluble metal oxide and its preparation method and application. The water-soluble metal oxide quantum dots prepared by the present invention have good antibacterial effect, low minimum inhibitory / bactericidal concentration for Escherichia coli and Staphylococcus aureus, and can play a bactericidal role in a short time.

[0006] The present invention provides a method for preparing water-soluble metal oxide quantum dots, comprising the following steps:

[0007] Mixing a metal salt, a low-grade alcohol solvent and a hydrophilic surfactant to obtain a metal salt mixture; the metal salt includes one or more of zinc salt, silver salt and copper salt;

[0008] The alkaline alcohol solution is added to the metal salt mixed solution, and the mixture is continuously stirred and the solid and liquid are separated to obtain water-soluble metal oxide quantum dots; the temperature of the continuous stirring is 50-55° C., and the time is 20-80 minutes.

[0009] Preferably, the metal salt comprises one or more of acetate, nitrate and sulfate.

[0010] Preferably, the lower alcohol solvent includes isopropanol or ethanol.

[0011] Preferably, the usage ratio of the metal salt to the lower alcohol solvent is 9-11 mmol:90-110 mL.

[0012] Preferably, the hydrophilic surfactant includes one or more of (3-aminopropyl)triethoxysilane, polyethylene glycol, sodium dodecylbenzene sulfonate and glycerol.

[0013] Preferably, the continuous stirring time is 40 to 60 minutes.

[0014] Preferably, the alkali source in the alkaline alcohol solution is an alkali metal hydroxide, and the alkali metal hydroxide includes one or more of sodium hydroxide, potassium hydroxide and lithium hydroxide.

[0015] Preferably, the molar ratio of the metal salt to the alkali source in the alkaline alcohol solution is 1:1 to 1:2.

[0016] The present invention also provides water-soluble metal oxide quantum dots obtained by the preparation method described in the above technical scheme, which are metal oxide quantum dots modified by a hydrophilic surfactant, including metal oxide quantum dots and a hydrophilic layer encapsulating the metal oxide quantum dots; the metal oxide quantum dots include one or more of zinc oxide, silver oxide and copper oxide.

[0017] The present invention also provides the use of the water-soluble metal oxide quantum dots described in the above technical solution in the preparation of antibacterial and bactericidal products.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] The present invention provides a method for preparing water-soluble metal oxide quantum dots, comprising the following steps:

[0020] Mixing a metal salt, a low-grade alcohol solvent and a hydrophilic surfactant to obtain a metal salt mixture; the metal salt includes one or more of zinc salt, silver salt and copper salt;

[0021] The alkaline alcohol solution is added to the metal salt mixed solution, and the mixture is continuously stirred to separate the solid and the liquid to obtain water-soluble metal oxide quantum dots; the continuous stirring time is 20 to 80 minutes.

[0022] The present invention controls the time of continuous stirring, that is, controls the time of compounding of metal oxide quantum dots and surfactants, through the sol-gel method, so that the obtained metal oxide has a small particle size and good hydrophilicity, thereby achieving a good antibacterial effect of the metal oxide quantum dots, a low minimum inhibitory / bactericidal concentration for Escherichia coli and Staphylococcus aureus, and can play a bactericidal role in a short time. The data of the embodiment show that the present invention controls the compounding time, and the synthesized water-soluble zinc oxide quantum dots have excellent antibacterial effect. The zinc oxide quantum dots formed within the compounding time of 20min to 80min have low minimum inhibitory concentration and minimum bactericidal concentration; when the zinc oxide quantum dots concentration is 256μg / mL, MRSAATCC43300 (1.0×10 5 CFU / mL) are all killed, and the sterilization effect is fast.

[0023] The metal oxide quantum dot nanomaterial prepared by the invention can generate ROS, has bactericidal and bacteriostatic effects, has good bactericidal effects on both Gram-positive bacteria and Gram-negative bacteria, and does not induce drug resistance. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0025] Figure 1 This is the transmission electron microscopy characterization image of water-soluble zinc oxide quantum dots (compounded for 80 minutes);

[0026] Figure 2 XRD of water-soluble zinc oxide quantum dots;

[0027] Figure 3 The results are for the bactericidal concentration of water-soluble zinc oxide quantum dots against Escherichia coli and Staphylococcus aureus;

[0028] Figure 4 The results are as follows: the bactericidal effect of water-soluble metal oxide quantum dots on MRSA;

[0029] Figure 5Development of water-soluble metal oxide quantum dots and levofloxacin resistance against multiple sublethal doses of Escherichia coli ATCC25922 and methicillin-resistant Staphylococcus aureus ATCC43300;

[0030] Figure 6 The results of DNA damage of water-soluble metal oxide quantum dots to MRSA;

[0031] Figure 7 It is the result of the destruction of bacterial cell membrane by water-soluble metal oxide quantum dots;

[0032] Figure 8 The water-soluble metal oxide quantum dots induce bacteria to produce superoxide. DETAILED DESCRIPTION

[0033] The present invention provides a method for preparing water-soluble metal oxide quantum dots, comprising the following steps:

[0034] Mixing a metal salt, a low-grade alcohol solvent and a hydrophilic surfactant to obtain a metal salt mixture; the metal salt includes one or more of zinc salt, silver salt and copper salt;

[0035] The alkaline alcohol solution is added to the metal salt mixed solution, and the mixture is continuously stirred and the solid and liquid are separated to obtain water-soluble metal oxide quantum dots; the temperature of the continuous stirring is 50-55° C., and the time is 20-80 minutes.

[0036] In the present invention, unless otherwise specified, the materials and equipment used are commercially available products in the art.

[0037] The invention mixes metal salt, low-grade alcohol solvent and hydrophilic surfactant to obtain metal salt mixed solution.

[0038] In the present invention, the metal salt preferably includes one or more of acetate, nitrate and sulfate, and more preferably zinc acetate dihydrate.

[0039] In the present invention, the lower alcohol solvent preferably includes isopropanol or ethanol.

[0040] In the present invention, the usage ratio of the metal salt to the lower alcohol solvent is preferably 9-11 mmol:90-110 mL, more preferably 10 mmol:100 mL.

[0041] In the present invention, the hydrophilic surfactant preferably includes one or more of (3-aminopropyl)triethoxysilane (APTES), polyethylene glycol, sodium dodecylbenzene sulfonate and glycerol, and the polyethylene glycol is preferably polyethylene glycol-200 (PEG-200).

[0042] In the present invention, the hydrophilic surfactant is preferably a liquid, and the volume ratio of the hydrophilic surfactant to the lower alcohol solvent is preferably 5-10:90-110, more preferably 5:100.

[0043] In the present invention, the mixing of the metal salt, the low-grade alcohol solvent and the hydrophilic surfactant is preferably as follows: the metal salt and the low-grade alcohol solvent are first mixed to obtain an alcohol solution of the metal salt, and then the hydrophilic surfactant is added for a second mixing; the first mixing is preferably carried out under stirring, the stirring temperature is preferably 65°C, and the time is preferably 20 minutes; the first mixing preferably also includes cooling, and the temperature after cooling is preferably 50°C; the second mixing temperature is preferably 50-55°C, and the time is preferably 10-25 minutes.

[0044] After obtaining the metal salt mixture, the present invention adds an alkaline alcohol solution to the metal salt mixture, continuously stirs, separates the solid and the liquid, and obtains water-soluble metal oxide quantum dots; the continuous stirring time is 20 to 80 minutes.

[0045] In the present invention, the alkali source in the alkaline alcohol solution is preferably an alkali metal hydroxide, and the alkali metal hydroxide preferably includes one or more of sodium hydroxide, potassium hydroxide and lithium hydroxide. The alkaline alcohol solution is preferably obtained by mixing an alkali metal hydroxide and an alcohol, and the mixing method is preferably ultrasonic dispersion; the alcohol preferably includes isopropanol or ethanol.

[0046] In the present invention, the usage ratio of the alkali source to the alcohol in the alkaline alcohol solution is preferably 9-11 mmol:90-110 mL, more preferably 10 mmol:100 mL.

[0047] In the present invention, the molar ratio of the metal salt to the alkali source in the alkaline alcohol solution is preferably 1:1 to 1:2, more preferably 1:1.

[0048] In the present invention, the temperature of the alkaline alcohol solution and the metal salt mixture during the addition is preferably 50-55° C., more preferably 50° C. The volume ratio of the alkaline alcohol solution to the metal salt mixture is preferably 1:1.

[0049] In the present invention, the addition is preferably completed within 30 seconds to avoid the generation of intermediate products due to too slow reaction.

[0050] In the present invention, the continuous stirring time is preferably 40 to 60 minutes, and during the continuous stirring process, the alkali metal salt and the alkali source react as follows:

[0051] Zn 2+ +OH - →[Zn(OH)] +

[0052] 2n[Zn(OH)] + →(ZnO)n+nZn 2+ +nH2O

[0053] (ZnO)n+2k[Zn(OH)] + →(ZnO) n+k +kZn 2+ +kH2O

[0054] Among them (ZnO) n Represents the crystal nucleus, (ZnO) n+k The quantum dots represent the quantum dots grown from the crystal nucleus, and the hydrophilic surfactant modifies the surface to form a hydrophilic layer. The continuous stirring time of the present invention forms the zinc oxide quantum dots with small particle size, good hydrophilicity and good antibacterial effect.

[0055] In the present invention, the solid-liquid separation method is preferably centrifugation, the centrifugal speed is preferably 4000 rpm, and the time is preferably 5 minutes. After the solid-liquid separation, it is preferred to further include: washing the obtained solid and drying, the washing reagent is preferably isopropanol, the drying temperature is preferably 40-60°C, and the time is preferably 48.

[0056] The present invention also provides water-soluble metal oxide quantum dots obtained by the preparation method described in the above technical solution, which are metal oxide quantum dots modified by a hydrophilic surfactant, comprising metal oxide quantum dots and a hydrophilic layer encapsulating the metal oxide quantum dots.

[0057] In the present invention, the water-soluble metal oxide quantum dots are preferably water-soluble zinc oxide quantum dots, and the particle size of the water-soluble zinc oxide quantum dots is preferably 5 to 10 nm.

[0058] The present invention also provides the use of the water-soluble metal oxide quantum dots described in the above technical solution in the preparation of antibacterial and bactericidal products.

[0059] The preparation method of the water-soluble metal oxide quantum dots provided by the present invention improves the water solubility and antimicrobial effect of the metal oxide quantum dots, has high antibacterial property, does not cause bacteria to develop drug resistance, and has a highly effective bactericidal effect on clinical drug-resistant bacteria. The present invention synthesizes water-soluble metal oxide quantum dots by a sol-gel method, and induces Gram-negative and Gram-positive bacteria for a long time in comparison with antibiotics, without causing drug resistance.

[0060] In order to further illustrate the present invention, the water-soluble metal oxide quantum dots and their preparation methods and applications provided by the present invention are described in detail below in conjunction with the accompanying drawings and examples, but they should not be construed as limiting the scope of protection of the present invention.

[0061] Example 1

[0062] 10 mmol of sodium hydroxide (NaOH) was dissolved in 100.0 mL of isopropanol, and the mixture was completely dispersed by ultrasonication and then heated to 50° C. to prepare a NaOH solution (Solution A).

[0063] 10 mmol of zinc acetate dihydrate was dissolved in 100.0 mL of isopropanol and stirred at 65°C for 20 min to prepare a metal salt solution, which was then cooled to 50°C to obtain solution B.

[0064] Then, 5 mL of polyethylene glycol 200 (i.e., PEG200) was added to solution B, and the mixture was stirred at 50°C for 10 minutes to obtain solution C. Solution A was then quickly (within 30 seconds) added to solution C at 50°C, and the mixture was stirred for 20 min, 40 min, 60 min, 80 min, 100 min, and 120 min (compounding time) to form an isopropanol solution (solution D) of metal oxide nanoparticles wrapped with a surfactant. 200 mL of water was added to solution D, and the mixture was centrifuged at 4000 rpm for 5 min, the supernatant was discarded, the precipitate was washed with isopropanol, the obtained nanoparticles were dried at 40°C for 48 h, and the dried solid was ground into a fine powder to obtain water-soluble zinc oxide quantum dots.

[0065] The obtained water-soluble zinc oxide quantum dots were observed by transmission electron microscopy and analyzed by XRD. Figure 1 Transmission electron microscopy characterization images of water-soluble zinc oxide quantum dots (compounded for 80 min) at different positions, and the scale length in the figure is 20 nm; Figure 2 This is the XRD of water-soluble zinc oxide quantum dots (compounded for 80 minutes). The synthesized surfactant-coated metal oxide nanoparticles are spherical with a particle size of 4 to 6 nm (mostly 5 nm). The XRD results show that the zinc oxide content in the synthesized zinc oxide quantum dots is relatively high, at 70 to 75%, proving that zinc oxide was successfully synthesized.

[0066] When the compounding time is 20 minutes, the particle size of the water-soluble zinc oxide quantum dots is 3 to 4 nm; when the compounding time is 40 minutes, the particle size is 3 to 4 nm; when the compounding time is 60 minutes, the particle size is 4 to 5 nm; when the compounding time is 100 minutes, the particle size is 6 to 8 nm; when the compounding time is 120 minutes, the particle size is 10 to 14 nm.

[0067] Test Example 1

[0068] Taking Escherichia coli, Staphylococcus aureus and clinically isolated drug-resistant bacteria as examples, the bactericidal and non-drug resistance effects of water-soluble metal oxide quantum dots were verified

[0069] 1. In vitro antibacterial test of metal oxide quantum dots synthesized by different methods

[0070] 1) Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)

[0071] First, 50 μL of glycerol culture of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) were cultured in 5 mL of LB liquid medium until the OD 600 = 0.6-0.8. Dilute the cultured bacterial solution to 2×10 5 CFU mL -1 The bacterial suspension was added to a 96-well plate, with a volume of 100 μL of bacterial suspension added to each well. Then different concentrations of water-soluble zinc oxide quantum dots were added (the final concentrations were 1024, 512, 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, and 0.25 μg mL -1 After incubation at 37°C for 16-18 hours, the MIC value is based on the clarification of the mixed solution in the wells visible to the naked eye.

[0072] Minimum bactericidal concentration (MBC): The final concentrations in the above 96-well microplate were 1024, 512, 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, and 0.25 μg mL -1 A volume of 100 μL of the mixed solution of water-soluble zinc oxide quantum dots was extracted, spread on an agar plate, and cultured in a 37°C incubator for 12 to 14 hours. The bacterial growth was observed and photographed. The final concentration of metal oxide quantum dots when the number of bacteria in each 100 μL volume was less than or equal to 5 colonies was taken as the MBC value.

[0073] Zinc oxide quantum dots with different synthesis methods (hydrothermal method, vapor phase precipitation method) were purchased from Taobao, with particle sizes of 40nm and 100nm respectively, and the above test was repeated. Table 1 shows the minimum inhibitory concentration and minimum bactericidal concentration of zinc oxide quantum dots with different synthesis methods against Escherichia coli (ATCC25922) and Staphylococcus aureus (ATCC25923). Figure 3 This is the bactericidal concentration result of water-soluble zinc oxide quantum dots (complexation time 80 min) against Escherichia coli and Staphylococcus aureus.

[0074] Table 1 Minimum inhibitory concentration and minimum bactericidal concentration of zinc oxide quantum dots synthesized by different methods against Escherichia coli (ATCC25922) and Staphylococcus aureus (ATCC25923)

[0075]

[0076] Compared with other synthesis methods (hydrothermal method, vapor phase precipitation method), the water-soluble metal oxide quantum dots prepared by the sol-gel method of the present invention have a highly effective bactericidal effect on standard strains. At the same time, it can be seen from Table 1 that the zinc oxide quantum dots with different compounding times have a great influence on the antibacterial performance, and the zinc oxide quantum dots formed within 20min to 80min have good antibacterial performance.

[0077] 2) Bactericidal kinetics curve

[0078] The standard strain of methicillin-resistant Staphylococcus aureus ATCC43300 was used as the test object. The bacterial suspension (about 1.0×10 5 CFU / mL) for 24 h. The viable colony counts were determined at different times during the incubation process. Three experiments were performed for each assay condition and the average value was recorded as the result.

[0079] Figure 4 This is the bactericidal effect of water-soluble metal oxide quantum dots on MRSA (the control in the figure is without quantum dots, only bacterial growth). The test results show that MRSAATCC43300 can be completely killed by 256μg / mL metal oxide quantum dots for 12 hours.

[0080] 2. Water-soluble metal oxide quantum dots induced drug resistance test

[0081] Escherichia coli ATCC25922 and methicillin-resistant Staphylococcus aureus ATCC43300 were used as model strains for resistance testing. Resistance was induced by repeated treatment of bacteria with sublethal doses of antimicrobial agents. In brief, ZnO@PEG200 QDs (complexation time 80min) and levofloxacin (control) were tested for 20 days of growth on Escherichia coli ATCC25922 and methicillin-resistant Staphylococcus aureus ATCC43300. The MIC was measured by using the above method. Escherichia coli ATCC25922 methicillin-resistant Staphylococcus aureus ATCC43300 with sub-MIC concentration (1 / 2 of the MIC in this particular generation) was regenerated and reached the logarithmic growth phase and then used for MIC measurement in the next generation. Development of resistance. The development of resistance in Escherichia coli ATCC25922 and methicillin-resistant Staphylococcus aureus ATCC43300 was evaluated by recording the changes in MIC normalized to the first cell passage.

[0082] Figure 5The water-soluble metal oxide quantum dots and levofloxacin resistance of Escherichia coli ATCC25922 and methicillin-resistant Staphylococcus aureus ATCC43300 were tested for multiple sublethal doses. The results showed that the broad-spectrum antibiotic levofloxacin would produce strong drug resistance in bacteria after long-term action, while the water-soluble metal oxide quantum dots prepared by the present invention would not produce drug resistance after repeated induction.

[0083] 3. Antibacterial effect of water-soluble metal oxide quantum dots on clinical drug resistance

[0084] Multiple drug-resistant bacteria isolated from clinical sites: MRSA, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii were cultured in liquid culture medium until the logarithmic growth phase and the growth rate was adjusted to 10 5 CFU / mL. 100 μL was added to a 96-well plate, and then different concentrations of water-soluble zinc oxide quantum dots were added (complexation time 80 min, final concentrations were 1024, 512, 256, 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25 μg mL -1 ). After being placed in a 37°C incubator for 16-18 hours, the MIC value is taken as the benchmark based on the clarification of the mixed solution in the well visible to the naked eye. At the same time, levofloxacin is used as an antibiotic control group. The MIC results show that the water-soluble metal oxide quantum dots synthesized by the present invention have an inhibitory effect on levofloxacin-resistant clinical strains compared with levofloxacin, and can play a higher inhibitory effect at a lower concentration.

[0085] Table 2 Minimum inhibitory concentration of water-soluble metal oxide quantum dots against clinical multidrug-resistant strains

[0086]

[0087]

[0088] 4. Antibacterial mechanism of water-soluble metal oxide quantum dots

[0089] 1) DNA damage

[0090] The bacterial suspension of MRSA cultured to the logarithmic growth phase was resuspended to a concentration of (10 8 CFU / mL) was added with a drug solution (water-soluble zinc oxide quantum dots prepared with a complexation time of 80 min in Example 1) to make the final concentration of the drug solution in the bacterial suspension 32, 64, and 128 μg / mL, and the medium without drug solution was used as a blank, and cultured in a shaker at 37°C for 12 h. Total nucleic acid was extracted using a bacterial DNA genome kit according to the instructions, and then identified using nucleic acid electrophoresis agar gel.

[0091] Figure 6 The results of water-soluble metal oxide quantum dots on MRSA DNA damage. Figure 6 It can be seen that water-soluble metal oxide quantum dots (32 μg / mL) have a damaging effect on bacterial nucleic acids.

[0092] 2) Membrane integrity test

[0093] 8-anilino-1-naphthalenesulfonic acid (ANS) was used as a fluorescent probe to measure changes in cell membrane fluidity. The bacterial suspension cultured to the logarithmic growth phase was washed three times with PBS and resuspended to a concentration of (10 8 CFU / mL) was added with a drug solution (water-soluble zinc oxide quantum dots prepared with a compounding time of 80 min in Example 1) to a final concentration of 4MIC, 2MIC, MIC, and 1 / 2MIC in the bacterial suspension, and PBS was used as a blank, and cultured in a shaker at 37°C for 12 hours. Then, the ANS fluorescent probe was added to the cell suspension at a fixed time point to a final concentration of 4 μmol / L, and incubated at 37°C in the dark for 15 minutes. The fluorescence intensity was then measured using a microplate reader (MK3, ThermoFisher) at an excitation wavelength of 385 nm and an emission wavelength of 473 nm.

[0094] Figure 7 This is the result of the water-soluble metal oxide quantum dots destroying the bacterial cell membrane. Figure 7 It can be seen that water-soluble metal oxide quantum dots can destroy the cell membrane of bacteria, causing the cell membrane to become fluid, leading to bacterial death, thereby producing a bactericidal effect.

[0095] 3) Determination of superoxide in bacteria

[0096] The intracellular · O2 - content. In short, dihydroethyl is dissolved in dimethyl sulfoxide. The bacteria and the mixed solution (LB medium containing water-soluble zinc oxide quantum dots prepared with a compounding time of 80 min in Example 1, with concentrations of 100 μg / mL and 200 μg / mL, respectively) were incubated at 37°C for 30 min. The bacteria were collected by centrifugation at 5000 rpm for 10 min and washed three times with PBS solution. The fluorescence intensity at 610 nm was immediately detected using a microplate reader (MK3, ThermoFisher).

[0097] Figure 8 The water-soluble metal oxide quantum dots cause bacteria to produce superoxide. The water-soluble metal oxide quantum dots will cause active oxygen to be produced in the bacteria, thereby producing superoxide, stimulating the bacteria to destroy themselves, thereby playing a bactericidal role.

[0098] Therefore, the water-soluble metal oxide quantum dots synthesized by the sol-gel method of the present invention have efficient bactericidal and antibacterial effects, and have better antibacterial effects than the hydrothermal method and the vapor precipitation method; in addition, the water-soluble metal oxide quantum dots not only have good antibacterial effects on clinical multi-drug resistant strains, but also do not cause bacterial resistance, and are an ideal alternative antibiotic material.

[0099] Although the above-mentioned embodiments have made a detailed description of the present invention, they are only some embodiments of the present invention, rather than all embodiments. People can also obtain other embodiments based on the embodiments of the present invention without creative work, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for preparing water-soluble metal oxide quantum dots, characterized in that: The following steps are involved: Mixing a metal salt, a low-grade alcohol solvent and a hydrophilic surfactant to obtain a metal salt mixture; the metal salt includes one or more of zinc salt, silver salt and copper salt; The alkaline alcohol solution is added to the metal salt mixed solution, and the mixture is continuously stirred and the solid and liquid are separated to obtain water-soluble metal oxide quantum dots; the temperature of the continuous stirring is 50-55° C., and the time is 20-80 minutes.

2. The preparation method according to claim 1, characterized in that: The metal salt includes one or more of acetate, nitrate and sulfate.

3. The preparation method according to claim 1, characterized in that: The lower alcohol solvent includes isopropanol or ethanol.

4. The preparation method according to claim 2 or 3, characterized in that: The usage ratio of the metal salt and the lower alcohol solvent is 9-11 mmol:90-110 mL.

5. The preparation method according to claim 1, characterized in that: The hydrophilic surfactant includes one or more of (3-aminopropyl)triethoxysilane, polyethylene glycol, sodium dodecylbenzene sulfonate and glycerol.

6. The preparation method according to claim 1, characterized in that: The continuous stirring time is 40 to 60 minutes.

7. The preparation method according to claim 1, characterized in that: The alkali source in the alkaline alcohol solution is an alkali metal hydroxide, and the alkali metal hydroxide includes one or more of sodium hydroxide, potassium hydroxide and lithium hydroxide.

8. The preparation method according to claim 1 or 7, characterized in that: The molar ratio of the metal salt to the alkali source in the alkaline alcohol solution is 1:1 to 1:

2.

9. The water-soluble metal oxide quantum dots obtained by the preparation method according to any one of claims 1 to 8, characterized in that: The invention is a metal oxide quantum dot modified by a hydrophilic surfactant, comprising a metal oxide quantum dot and a hydrophilic layer encapsulating the metal oxide quantum dot; the metal oxide quantum dot comprises one or more of zinc oxide, silver oxide and copper oxide.

10. Use of the water-soluble metal oxide quantum dots according to claim 9 in the preparation of antibacterial and bactericidal products.

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