CN107971481A - Gold nanoclusters with antibacterial activity and its preparation method and application - Google Patents

Gold nanoclusters with antibacterial activity and its preparation method and application Download PDF

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Publication number
CN107971481A
CN107971481A CN201610921679.7A CN201610921679A CN107971481A CN 107971481 A CN107971481 A CN 107971481A CN 201610921679 A CN201610921679 A CN 201610921679A CN 107971481 A CN107971481 A CN 107971481A
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gold nanoclusters
glutathione
gold
antibacterial
preparation
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CN107971481B (en
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蒋兴宇
谢阳州昀
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National Center for Nanosccience and Technology China
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National Center for Nanosccience and Technology China
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    • B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
    • B22F1/10—Metallic powder containing lubricating or binding agents; Metallic powder containing organic material
    • B22F1/102—Metallic powder coated with organic material
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    • A61K33/00—Medicinal preparations containing inorganic active ingredients
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    • B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
    • B22F9/24—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds starting from liquid metal compounds, e.g. solutions
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    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Abstract

The present invention provides a kind of gold nanoclusters with antibacterial activity, wherein, the gold nanoclusters are only modified by glutathione or modified by glutathione and thiol ligand, the thiol ligand is sulfydryl doped quaternary ammonium salt, cell-penetrating peptide and its derivative or mercaptopyrimidine, and the molar content ratio of gold element and the glutathione is 1.2~2:1, the particle diameter of the gold nanoclusters is less than 2nm.The gold nanoclusters have easy preparation method, good biocompatibility and outstanding antibacterial activity.Present invention also offers the preparation method and application of the gold nanoclusters, and bactericidal composition, antibacterial combination product or antibiotic paint comprising the gold nanoclusters.

Description

Gold nanoclusters with antibacterial activity and its preparation method and application
Technical field
The present invention relates to a kind of gold nanoclusters, more particularly to a kind of gold nanoclusters with antibacterial activity, and its gold The preparation method and application of nano-cluster, and bactericidal composition or antibiotic paint comprising the gold nanoclusters.
Background technology
For a long time, bacterium infection is always to threaten a major disease of human health, in the 1940s, the mankind Antibiotic is invented to be used for bacterial-infection resisting, has greatly reduced due to malpractice caused by bacterium infection.However, in recent years With the abuse of antibiotic, some new multidrug resistance bacteriums gradually appear, and some bacteriums are even developed unprecedented The resistance to the action of a drug.These bacteriums will not be killed by current commercialized antibiotic, be referred to as superbacteria.With going out for superbacteria Existing, bacterium infection becomes a significant threat of human health again.People caused by the super medicine bacterium of many developed economies Mouth is dead to exceed 2/3rds of annual total death population.We are tighter to solve about to come there is an urgent need for some effective schemes The superbacteria phenomenon of weight.
In recent years, flourishing due to nanometer technology, more and more nano material synthesis are used as antiseptic.Its Middle copper nano particles, metal oxide nanoparticles and silver nano-grain etc. have larger toxicity.In addition, some carbon materials include Fullerene, graphene etc. are also found to have certain antibacterial activity.But these particles are often relatively low with antibacterial activity Defect.Some nano titania particles and gold nanorods are recognized as with the prospect as antibiotic layer, but these nanometer of material Material just has antibacterial activity only under the booster action of laser.
Therefore, good biocompatibility, it is of low cost, have antibacterial activity especially Multidrug resistant bacteria antibacterial activity is resisted Bacterium medicine is still the emphasis of scientific research personnel's research.
The content of the invention
Therefore, based on prior art the defects of, it is an object of the invention to provide a kind of gold nano with antibacterial activity Cluster, and its preparation method and application of the gold nanoclusters, and the bactericidal composition comprising the gold nanoclusters or antibacterial apply Material.
To achieve these goals, the present invention provides technical solution in detail below：
On the one hand, the present invention provides a kind of gold nanoclusters (AuNCs) with antibacterial activity, wherein, the gold nanoclusters Only modified by glutathione (GSH) or modified by glutathione and thiol ligand, the thiol ligand is sulfydryl doped quaternary ammonium salt (QA), The molar content ratio of cell-penetrating peptide and its derivative or mercaptopyrimidine, gold element and the glutathione is 1.2~2:1, the gold The particle diameter of nano-cluster is less than 2nm.
Preferably, the glutathione and/or the thiol ligand are modified to the gold nanoclusters table by fabricated in situ Face, and/or the glutathione and/or the thiol ligand pass through Au-S key connections to the gold nanoclusters surface.
Gold nanoclusters according to a first aspect of the present invention, wherein, the thiol ligand and the glutathione mole contain Amount is than being 1~10:1, it is preferably 1:1、2:1、5:1 or 10:1.
Gold nanoclusters according to a first aspect of the present invention, wherein, the sulfydryl doped quaternary ammonium salt is long alkane chain doped quaternary ammonium salt or generation The doped quaternary ammonium salt of phenyl ring.Gold nanoclusters according to a first aspect of the present invention, wherein, the cell-penetrating peptide and its derivative are poly essence ammonia Acid or TAT protein, more poly arginines are preferably the small peptide of eight to two ten arginine compositions, are most preferably nine poly arginines (R9).Gold nanoclusters according to a first aspect of the present invention, wherein, the mercaptopyrimidine is 2,4-2 amino-2-mercapto phenyl formic pyrimidines (DAPT) or 2- sulfydryl -4- amino -6- hydroxy pyrimidines.
On the other hand, the present invention provides a kind of system for being used to prepare the foregoing fluorescence gold nanoclusters only modified by glutathione Preparation Method, it is used to prepare the fluorescence gold nanoclusters of the first invention of the present invention, the described method includes：(1) according to proportioning, chlorine is mixed Auric acid and glutathione obtain mixed liquor, and the mixed liquor of (2) heated at constant temperature step (1) obtains the gold nanoclusters.Preferably, institute The temperature for stating heated at constant temperature is 40~120 DEG C, more preferably 50~100 DEG C, is most preferably 70 DEG C；And/or the heated at constant temperature Time be 12~48h, be preferably 18~30h, be most preferably 24h.
Another aspect, present invention offer is a kind of to be used to prepare the foregoing fluorogold modified by glutathione and thiol ligand Nano-cluster, the described method includes：(a) according to proportioning, mixing gold chloride (HAuCl4), glutathione and thiol ligand mixed Liquid, the mixed liquor of (b) heated at constant temperature step (a) obtain the gold nanoclusters.Preferably, the temperature of the heated at constant temperature for 40~ 120 DEG C, more preferably 50~100 DEG C, are most preferably 70 DEG C；And/or the time of the heated at constant temperature is 12~48h, it is preferably 18~30h, is most preferably 24h.
Another further aspect, the present invention provide a kind of foregoing gold nanoclusters or are existed according to gold nanoclusters prepared by aforementioned preparation process Prepare the application in the medicine or medical product for antibacterial；Preferably, the targeted bacterium of the antibacterial is thin for multidrug resistance Bacterium.
According to foregoing application, the targeted bacterium of the antibacterial is Gram-negative bacteria, it is preferable that the leather is blue Family name's negative bacterium is selected from：Shigella dysenteriae, typhoid bacillus, Escherichia coli, proteus, Pseudomonas aeruginosa, Bordetella pertussis, comma bacillus And diplococcus meningitidis.
According to foregoing application, the targeted bacterium of the antibacterial is gram-positive bacteria, it is preferable that the leather is blue Family name's positive bacteria is selected from：Staphylococcus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, corynebacterium diphtheriae and clostridium tetani.
Another aspect, the present invention provide a kind of foregoing gold nanoclusters or are existed according to gold nanoclusters prepared by aforementioned preparation process Prepare medicine or the medical treatment production for being used to prevent and/or treat by Gram-negative bacteria and/or the microbial illness of Gram-positive Application in product；
Preferably, the illness is selected from following one or more：Infection of skin and subcutaneous tissue, wound infection, middle ear Inflammation, meningitis, peritonitis, enteritis, bronchitis, pneumonia, respiratory tract infection, urinary system infection contamination, septicemia and pyemia.
Further aspect, the present invention provide a kind of bactericidal composition, antibacterial combination product or antibiotic paint, the antibacterial combination Thing, antibacterial combination product or antibiotic paint include any foregoing gold nanoclusters or the gold nano prepared according to aforementioned preparation process Cluster, the antibacterial combination product is preferably kit form.
An embodiment according to the present invention, antibacterial of the present invention are anti-Gram-negative bacteria and/or gram sun Property bacterium.Wherein, the Gram-negative bacteria is preferably selected from shigella dysenteriae, typhoid bacillus, Escherichia coli, proteus, green pus bar One or more in bacterium, Bordetella pertussis, comma bacillus and diplococcus meningitidis, the gram-positive bacteria are preferably selected from One or more in staphylococcus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, corynebacterium diphtheriae and clostridium tetani.
An embodiment according to the present invention, drug resistant Gram-negative bacteria of the present invention and/or Gram-positive Bacterium is the Gram-negative bacteria and/or gram-positive bacteria that tolerance is produced to corresponding antibiotic.Such as Gram-positive Drug-fast bacteria staphylococcus aureus (MRSA), Gram-positive drug-fast bacteria streptococcus, the anti-Escherichia coli of Gram-negative drug-fast bacteria (MDR E.coli) or Gram-negative drug-fast bacteria Pseudomonas aeruginosa.
An embodiment according to the present invention, the present invention is in the preparation process of gold nanoclusters, by adjusting GSH and not With the ratio of thiol ligand, the gold nanoclusters of first aspect present invention can be the single gold nanoclusters (GSH- modified by GSH AuNCs), the molar content of GSH and sulfydryl doped quaternary ammonium salt ratio is 1:1 QA1-AuNCs, GSH and the molar content of sulfydryl doped quaternary ammonium salt Than for 1:5 QA5-AuNCs, GSH and the molar content ratio of sulfydryl doped quaternary ammonium salt are 1:10 QA10-AuNCs, the poly- essences of GSH and nine The molar content ratio of propylhomoserin is 1:1 R9The molar content of 1-AuNCs, GSH and nine poly arginines ratio is 1:2 R92-AuNCs、 The molar content of GSH and nine poly arginines ratio is 1:5 R9The molar content of 5-AuNCs, GSH and TAT protein ratio is 1:1 The molar content of TAT1-AuNCs, GSH and TAT protein ratio is 1:2 TAT2-AuNCs, GSH and the molar content ratio of TAT protein For 1:The molar content ratio of 5 TAT5-AuNCs, GSH and DAPT are 1:The molar content of 1 DAPT1-AuNCs, GSH and DAPT Than for 1:5 DAPT5-AuNCs or GSH and the molar content ratio of DAPT are 1:10 DAPT10-AuNCs.The gold nanoclusters Most of excitations at 430nm can send the feux rouges of more than 600nm and/or can enter cell and bacterium in electropositive.
Relative to the prior art, gold nanoclusters provided by the present invention have easy preparation method, good biofacies Capacitive and outstanding antibacterial activity.The preparation method being related to is simple, reaction condition it is very gentle (room temperature, normal pressure, water phase and PH near neutrals), and can largely prepare rapidly, be conducive to the gold nanoclusters and be applied to biology or medicine aspect.Synthesis Ligand on gold nanoclusters is all by chemical key connection, than what is connected in the past by ligand exchange with the methods of Electrostatic Absorption More close, so gold nanoclusters can more be stablized, significant change can't be occurred by being stored at room temperature more than 1 year property.It is described The good antibacterial activity and biocompatibility of gold nanoclusters have widened its research in antibiotic, antiseptic and antibiotic paint.
Brief description of the drawings
Hereinafter, the embodiment that the present invention will be described in detail is carried out with reference to attached drawing, wherein：
Fig. 1 shows that QA-AuNCs and DAPT-AuNCs are thin in melanoma cells (A375) and human umbilical vein endothelial The cytotoxicity of born of the same parents (HUVEC)；
Fig. 2 shows the hemolytic experiment data of the QA-AuNCs of test example 5；
Fig. 3 shows the SEM figures of test example 6.
Embodiment
The present invention is further illustrated below by specific embodiment, it should be understood, however, that, these embodiments are only It is used for specifically describing in more detail, and is not to be construed as limiting the present invention in any form.
This part carries out general description to the material and test method that are arrived used in present invention experiment.Although it is Realize that many materials used in the object of the invention and operating method are it is known in the art that still the present invention still uses up herein It may be described in detail.It will be apparent to those skilled in the art that within a context, if not specified, material therefor of the present invention and behaviour It is well known in the art as method.
The reagent and instrument used in following embodiments is as follows：Reagent：
Gold chloride, purchased from Sinopharm Chemical Reagent Co., Ltd.；Sulfydryl doped quaternary ammonium salt, nine poly arginines, mercaptopyrimidine purchase It is biochemical from Shanghai gill, scorching happy biological Co., Ltd, strong credit biology.
Instrument：
Fluorescence Spectrometer, purchased from Shimadzu, Japan, model RF-5301PC；
Inductive coupling plasma emission spectrograph (ICP-OES), purchased from beautiful Pekin-Elmer companies, model Optima 5300DV；
Nano particle size and Zeta potential analyzer (NZS), purchased from Malvern Instr Ltd. of Britain, model Zetasizer Nano ZS；
Lanthanum hexaboride transmission electron microscope (T-20), purchased from FEI Co. of the U.S., 20 S-TWIN of model Tecnai G2.
Embodiment 1
The present embodiment is used to illustrate gold nanoclusters of the present invention and preparation method thereof.
Comprise the following steps that：
(1) mix the gold chloride that 300 μ l concentration are 120mM and the glutathione that 10ml concentration is 3mM obtain mixed liquor,
The mixed liquor of step (1) obtains the gold nanoclusters, i.e., the Jenner of single GSH modifications when (2) 70 DEG C of heating 24 are small Rice cluster (GSH-AuNCs),
Embodiment 2
The present embodiment is used to illustrate gold nanoclusters QA1-AuNCs of the present invention and preparation method thereof.
Comprise the following steps that：
(1) mix 300 μ l concentration be 120mM gold chloride, 10ml concentration be 0.3mM sulfydryl doped quaternary ammonium salt and 10ml concentration Mixed liquor is obtained for the glutathione of 3mM,
The mixed liquor of step (1) obtains the gold nanoclusters, i.e. GSH and sulfydryl doped quaternary ammonium salt when (2) 70 DEG C of heating 24 are small Molar content ratio is 1:1 QA1-AuNCs,
Embodiment 3
The present embodiment is used to illustrate gold nanoclusters QA5-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 4
The present embodiment is used to illustrate gold nanoclusters QA10-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 5
The present embodiment is used for the gold nanoclusters R for illustrating the present invention91-AuNCs and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 6
The present embodiment is used for the gold nanoclusters R for illustrating the present invention92-AuNCs and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 7
The present embodiment is used for the gold nanoclusters R for illustrating the present invention95-AuNCs and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 8
The present embodiment is used to illustrate gold nanoclusters TAT1-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 9
The present embodiment is used to illustrate gold nanoclusters TAT2-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 10
The present embodiment is used to illustrate gold nanoclusters TAT5-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 11
The present embodiment is used to illustrate gold nanoclusters DAPT1-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 12
The present embodiment is used to illustrate gold nanoclusters DAPT5-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
Embodiment 13
The present embodiment is used to illustrate gold nanoclusters DAPT10-AuNCs of the present invention and preparation method thereof.
The preparation method of the present embodiment is substantially the same manner as Example 2, differs only in the thiol ligand specified by table 1 below And prepared by thiol ligand concentration.
The thiol ligand and its thiol ligand concentration of 1 embodiment 1~13 of table
Test example 1
This test example is used for the physicochemical properties for studying the gold nanoclusters prepared by embodiment 1~13.
1. use the fluorescence of Fluorescence Spectrometer test synthetic material
2. use gold dollar cellulose content of the inductive coupling plasma emission spectrograph measure for antibacterial experiment gold nanoclusters (μg/ml)。
3. use the size and current potential of nano particle size and Zeta potential analysis-e/or determining material.
4. it is used for the appearance for observing gold nanoclusters using lanthanum hexaboride transmission electron microscope.
Result of the test such as following table.
The physicochemical properties of 2 embodiment 1~13 of table
2 antibacterial activity test of test example
This test example is used for the antibacterial activity for studying embodiment 1~13.
Antibacterial activity is embodied by minimal inhibitory concentration, minimum antibacterial dense using micro-dilution method or orifice plate Dilution Degree.
Specific test method is as follows：
1. using 96 orifice plate of sterile transparent, it is grouped first, every group of first hole is maximum concentration sample Group, volume are 200 μ L, and concentration is 320 μ g/mL.
2. remaining each hole is separately added into 100 μ L culture mediums, then the first boreliquid is taken out in the second hole of 100 μ L additions and is mixed Even, sample concentration is 160 μ g/mL.Each hole carries out doubling dilution successively in a similar fashion below, until second from the bottom group, After mixing, directly take out 100 μ L and discard.Last hole is negative control group, and sample concentration is 0 μ g/mL.
3. by Bacteria Culture to logarithmic phase, bacteria concentration is adjusted to 1 × 10 with culture medium5CFU/mL, adds on 10 μ L per hole Bacterium solution is stated, then orifice plate is placed in 37 degree of constant incubator and cultivates 24h.Each concentration be all provided with three it is parallel.
4. the turbidity in each hole of observation, the minimum sample concentration corresponding to the hole that solution is transparent, not muddy is most Small Mlc.
Experimental result see the table below.
The minimal inhibitory concentration (μ g/ml) of 3 embodiment 1~13 of table
It is preferable to the gold that doped quaternary ammonium salt and mercaptopyrimidine are modified for antibacterial effect in a series of gold nanoclusters of synthesis Nano-cluster.
The gold nanoclusters QA10-AuNCs of doped quaternary ammonium salt modification includes Gram-negative bacteria shigella dysenteriae, typhoid bacillus, big The minimum inhibitory concentrations such as enterobacteria, proteus, Pseudomonas aeruginosa, Bordetella pertussis, comma bacillus and diplococcus meningitidis are reachable To 20-40 μ g/mL, 20-40 μ g/mL are can reach for drug resistant Gram-negative bacteria minimum inhibitory concentration.
QA10-AuNCs includes staphylococcus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, diphtheria bar to Lan Shi positive bacterias The minimum inhibitory concentration of bacterium, clostridium tetani etc. can reach 2.5-10 μ g/mL, minimum antibacterial for drug resistant gram-positive bacteria Concentration can reach 5-10 μ g/mL.
The gold nanoclusters DAPT10-AuNCs of mercaptopyrimidine modification includes shigella dysenteriae, typhoid fever bar to Gram-negative bacteria The minimum inhibitory concentrations such as bacterium, Escherichia coli, proteus, Pseudomonas aeruginosa, Bordetella pertussis, comma bacillus and diplococcus meningitidis 5-20 μ g/mL are can reach, 5-20 μ g/mL are can reach for drug resistant Gram-negative bacteria minimum inhibitory concentration.QA10-AuNCs Staphylococcus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, corynebacterium diphtheriae, clostridium tetani etc. are included most to Lan Shi positive bacterias Low Mlc can reach 10-20 μ g/mL, and 10-20 μ g/ are can reach for drug resistant gram-positive bacteria minimum inhibitory concentration mL。
Thus, it could be seen that the gold nanoclusters of synthesis have good antibacterial activity to a variety of sensitive and drug-fast bacterias, it is a kind of latent The candidate's antiseptic being used for antimicrobial agent, even superbacteria.
The contrast test of test example 3 and an existing line antibacterials
Antibacterial activity is embodied by minimal inhibitory concentration, minimum antibacterial dense using micro-dilution method or orifice plate Dilution Degree.
Specific test method is same as Example 2.
Result of the test such as table 4 below~6：
Table 4
Table 5
Table 6
The antibacterial activity of experiment discovery AuNCs difference compared with common antibacterials is little.
4 cytotoxicity test of test example
Two kinds of cells of selection are tested, and are melanoma cells (A375) and human umbilical vein endothelial cell respectively (HUVEC)。
DAPT-AuNCs prepared by the QA-AuNCs and embodiment 13 that sample to be tested is prepared for embodiment 4.
Specific test method is as follows：
1. taking 96 orifice plates of sterile transparent, 5000 cells are accessed in each hole.When cell growth 24 is small
2. the concentration of sample to be tested from 320 μ g/mL are diluted step by step with 2 times.The sample to be tested of 10 μ L various concentrations is added Enter and be incubated 24h altogether with cell into 96 orifice plates.
3. into 96 orifice plates of step 2, each hole adds CCK8 reagents (being purchased from green skies biotech company), as reality Test group；Take 96 orifice plates of same specification and add culture medium and CCK8 reagents, as blank group；Take 96 orifice plates of same specification and add Cell and CCK8 reagents, as negative control group.
4. the OD450 values in test cell nutrient solution.The OD450 values of gold nanoclusters can be ignored.Cell viability= (experimental group-blank)/(control group-blank) * 100%.
Result of the test such as Fig. 1.
The result shows that the antibiotic layer of antibacterial product of the invention does not all have toxicity to these cells, cell survival rate exists Between 95~105%.
5 haemolysis of test example is tested
Sample to be tested is gold nanoclusters prepared by embodiment 4.
Specific test method is as follows：
1. the preparation of blood cell suspension：Take people's blood 5mL to be put into conical flask, blood constantly stirred with glass bar, with except Defibrinate original.About 10 times of amounts of 0.9% sodium chloride solution are added, are mixed, 1200r/min is centrifuged 15 minutes, removes supernatant, The red blood cell precipitated.Washed again with 0.9% sodium chloride solution untill the not aobvious red of supernatant.Gained red blood cell is used 0.9% sodium chloride solution is made into 2% suspension, stand-by.
2. experimental implementation：Clean centrifuge tube 5, numbering 1 to 5 are taken, No. 1-3 pipe is addition various concentrations sample to be tested (100,20,5 μ g/ml), No. 4 pipes are negative control pipe, and No. 5 pipes are positive control pipe (Triton).It is separately added into 2% red blood cell Suspension, after mixing, places be incubated in 37 degree of insulating box immediately.After just having started when observation in 15 minutes 1 time, 1 is small, every 1 Hour observation 1 time, 3 it is small when after test.
3. result is observed：After 3 are incubated when small, centrifuged 15 minutes with 1200r/min, recording photograph is simultaneously divided with UV, visible light Light absorption value at photometer test 540nm.
Result of the test such as Fig. 2.
This test finds that the gold nanoclusters will not produce blood coagulation phenomenon while antibacterial.
The processing ne ar change of 6 electron microscope observation gold nanoclusters of test example
DAPT-AuNCs gold nanoclusters prepared by the QA-AuNCs and embodiment 13 that sample to be tested is prepared for embodiment 4.
The sample preparation of scanning electron microscope SEM observation AuNCs processing ne ar changes：
1. staphylococcus aureus or Escherichia coli culture are collected thalline, use PBS to logarithmic phase, 8000rpm centrifugations min Buffer solution is washed once.Gold nanoclusters are added into the bacterium solution of same volume so that the final concentration of 10 μ g/mL of material, solution Final volume is 2mL.Gold nanoclusters are incubated 3h with bacterium under 37 degree.The bacterial solution for being not added with gold nanoclusters is control group (control)。
Thalline is collected by centrifugation after being incubated in 2.3h, and thalline is washed once with PB buffer solutions.Add 500L's 2.5% into thalline Glutaraldehyde fixer, soaks 24h.
3. being washed three times with PBS buffer, taken off successively with 30%, 50%, 70%, 90%, 95%, 100% ethanol afterwards Water 15min.100% ethanol is removed, thalline is transferred on silicon chip, is dried, is changed with SEM observation ne ars.
Result of the test is shown in Fig. 3, represents that the form of Escherichia coli and staphylococcus aureus is adding QA-AuNCs and DAPT- Change later AuNCs.
The sample preparation of transmission electron microscope tem observation gold nanoclusters processing ne ar change：
1. prepare spurr epoxy resin.Curing agent (nonenyl succinic acid acid anhydride NSA) is separately added into the centrifuge tube of 50mL 25g, epoxy plasticizer (ethylene dioxide base cyclohexene ERL 4221) 10g, polyglycol type epoxy resins (DER 736) 8g, most After add appropriate curing accelerator (dimethylaminoethanol DMAE), rapidly stir 3 minutes bubble removings.The resin prepared is freezed Preserve, it is stand-by.
2. carry out the preparation of bacteria samples.Staphylococcus aureus is cultivated into-logarithmic phase, 8000rpm centrifugations 3min Thalline is collected, is washed once with PBS buffer.Add gold nanoclusters into the bacterium solution of same volume so that material it is final concentration of 10 μ g/mL, the final volume of solution is 2mL.Gold nanoclusters are incubated 3h with bacterium under 37 degree.It is not added with the bacterial solution of TBA-TPE For control group.
Thalline is collected by centrifugation after being incubated in 3.3h, and thalline is washed once with PBS buffer.Add 500 L's 2.5% to thalline Glutaraldehyde fixer, fixed 24h.Washed three times with PBS buffer, afterwards with 30%, 50%, 70%, 90%, 95%, 100% Ethanol is dehydrated 15min successively.
4. removing 100% ethanol, thalline is placed under room temperature.Acetone leaching is added into the bacteria samples prepared 15min is steeped, uses epoxy resin successively afterwards：Acetone is 1：3、1：1、3：1 processing 2h.Then 2.5h is incubated with epoxy resin, then Remove epoxy resin.Bacterium sample is transferred to mould, epoxy resin to die hole is added and fills up, de-bubble.Sample is placed in 70 DEG C of bakings Cure 15h in case.Sample is thinly sliced into (thickness 60-70nm) with slicer, is placed on transmission electron microscope copper mesh.Sample sections Bimetallic (uranium acetate and lead citrate) dyeing is carried out, is changed with transmission electron microscope observation bacterium pattern.
7 animal toxicity test of test example
Single-dose is tested：
Sample to be tested is QA-AuNCs gold nanoclusters prepared by embodiment 4.
1. configure various concentrations AuNCs normal saline solutions (6400 μ g/Kg, 3200 μ g/Kg, 1600 μ g/Kg, 800 μ g/ Kg、400μg/Kg、200μg/Kg、100μg/Kg、50μg/Kg、25μg/Kg)
2. give 100 μ of every mouse tail vein injection various concentrations AuNCs normal saline solution and simple normal saline solution L.Wherein simple normal saline solution (control group).
Mouse survival rate when 3. observation 48 is small, and record.Every group of mouse 5, experiment is repeated 3 times.
Multiple dosing is tested：
Sample to be tested is QA-AuNCs gold nanoclusters prepared by embodiment 4.
1. configure various concentrations AuNCs normal saline solutions (6400 μ g/Kg, 3200 μ g/Kg, 1600 μ g/Kg, 800 μ g/ Kg、400μg/Kg、200μg/Kg、100μg/Kg、50μg/Kg、25μg/Kg)
2. give 100 μ of every mouse tail vein injection various concentrations AuNCs normal saline solution and simple normal saline solution L.Wherein simple normal saline solution (control group).
3. mouse survival rate is observed and recorded when 48 is small, and repeat administration.Cultivate mouse 28 days.Every group of mouse 5, it is real Test and be repeated 3 times.
Experimental result is：
Single-dose：Injecting normal saline group mouse all survives.Injecting the AuNCs of 3200 μ g/kg can make mouse whole Survival, mouse occurs dead if incremental dose.
Multiple dosing：Injecting normal saline group mouse all survives.Injecting the AuNCs of 1600 μ g/kg can make mouse whole Survival, mouse occurs dead if incremental dose.
Antibacterial effect is tested in 8 body of test example
Sample to be tested is QA-AuNCs gold nanoclusters prepared by embodiment 4.
Mouse peritoneal bacterial infection model is built first：
1. cultivating bacterium to logarithmic phase, thalline is collected by centrifugation, twice is washed with physiology salt, afterwards with physiological saline by thalline It is diluted to 6 × 105CFU/mL。
It is 2. stand-by with yeast (Angel Yeast) solution of physiological saline configuration 10%, sterilizing.Bacterium solution and yeast soln are with body Product ratio 1:1 mixing is used as mouse peritoneal parenteral solution.Every mouse peritoneal injects 500 μ L dilution bacterium solutions, gently rubs mouse web portion, builds Murine Model of Intraperitoneal Infection model.
3. after half an hour, tail vein injection the first pin various concentrations AuNCs normal saline solutions, simple physiology salt are water-soluble Liquid, kanamycins or Norfloxacin normal saline solution and 100 μ L of vancomycin or roxithromycin normal saline solution.8 it is small when Afterwards, the second pin of tail vein injection various concentrations AuNCs normal saline solutions (400 μ g/Kg, 200 μ g/Kg, 100 μ g/Kg), simple Normal saline solution (negative control), kanamycins normal saline solution (negative control) and vancomycin normal saline solution (positive control) 100 μ L.
Mouse survival rate when 4. observation 48 is small, and record.Every group of mouse 5, experiment is repeated 3 times.
It is typical Gram-positive drug-fast bacteria MRSA and typical Gram-negative drug-fast bacteria MDR to test the bacterium used E,coli。
Experimental result is：In MRSA bacterial infection models, injecting normal saline group mouse after bacterium infection due to not having Antibiosis extract for treating, it is all dead.Kanamycins group mouse is injected, since bacterium is that kanamycins is drug resistant, mouse treatment Effect is also very undesirable, only 1 survival.Vancomycin group mouse is injected, since bacterium is vancomycin sensitive, is had very Good therapeutic effect, mouse all survive.Injecting the AuNCs of 400 μ g/kg can make mouse all survive, if dosage is lowered Therapeutic effect declines, it is seen that the therapeutic effect of the AuNCs antiseptics is dose-dependent.Ensure the AuNCs that mouse all survives Dose ratio commercialization antibiotic vancomycin is low.AuNCs has the effect of good internal confrontation resistant Staphylococcus aureus, is A kind of potential candidate's antiseptic being used for antimicrobial agent, even superbacteria.
In MDR E, coli bacterial infection models, injecting normal saline group mouse after bacterium infection due to not having antibiotic Treatment, it is all dead.Inject Norfloxacin group mouse, since bacterium is that Norfloxacin is drug resistant, mouse therapeutic effect It is very undesirable.Vancomycin group mouse is injected, since bacterium is roxithromycin sensitivity, there is good therapeutic effect, mouse All survivals.Injecting the AuNCs of 400 μ g/kg can make mouse all survive, and therapeutic effect declines if dosage is lowered, it is seen that The therapeutic effect of the AuNCs antiseptics is dose-dependent.Ensure AuNCs dose ratio commercialization antibiotic sieve that mouse all survives Erythromycin is low.AuNCs has the effect of good internal confrontation antibiotic-resistance E. coli, is that one kind is potentially used for overriding resistance Candidate's antiseptic of bacterium, even superbacteria.
Although present invention has been a degree of description, it will be apparent that, do not departing from the spirit and scope of the present invention Under the conditions of, the appropriate change of each condition can be carried out.It is appreciated that the invention is not restricted to the embodiment, and it is attributed to right It is required that scope, it includes the equivalent substitution of each factor.

Claims (10)

  1. A kind of 1. gold nanoclusters with antibacterial activity, it is characterised in that the gold nanoclusters only by glutathione modify or by Glutathione and thiol ligand modification, the thiol ligand be sulfydryl doped quaternary ammonium salt, cell-penetrating peptide and its derivative or mercaptopyrimidine, golden The molar content of element and glutathione ratio is 1.2~2:1, the particle diameter of the gold nanoclusters is less than 2nm, it is preferable that institute State glutathione and/or the thiol ligand and pass through fabricated in situ modification to the gold nanoclusters surface, and/or the gluathione Peptide and/or the thiol ligand pass through Au-S key connections to the gold nanoclusters surface.
  2. 2. gold nanoclusters according to claim 1, it is characterised in that the gold nanoclusters are by glutathione and thiol ligand Modification；Preferably, the thiol ligand and the molar content of glutathione ratio are 1~10:1, more preferably 1:1、2:1、 5:1 or 10:1.
  3. 3. gold nanoclusters according to claim 2, it is characterised in that
    The sulfydryl doped quaternary ammonium salt is long alkane chain doped quaternary ammonium salt or the doped quaternary ammonium salt for phenyl ring；
    The cell-penetrating peptide and its derivative are more poly arginines or TAT protein, and more poly arginines are preferably eight to two ten The small peptide of arginine composition, is most preferably nine poly arginines；And/or
    The mercaptopyrimidine is 2,4-2 amino-2-mercapto phenyl formics pyrimidine or 2- sulfydryl -4- amino -6- hydroxy pyrimidines.
  4. 4. the preparation method of the gold nanoclusters only modified by glutathione described in a kind of claim 1, it is characterised in that described Method includes：
    (1) according to proportioning, mix gold chloride and glutathione obtain mixed liquor,
    (2) mixed liquor of heated at constant temperature step (1) obtains the gold nanoclusters；
    Preferably, the temperature of the heated at constant temperature is 40~120 DEG C, more preferably 50~100 DEG C, is most preferably 70 DEG C, and/or
    The time of the heated at constant temperature is 12~48h, is preferably 18~30h, is most preferably 24h.
  5. A kind of 5. preparation of the gold nanoclusters modified by glutathione and thiol ligand any one of claims 1 to 3 Method, it is characterised in that the described method includes：
    (a) mixed liquor is obtained according to proportioning, mixing gold chloride, glutathione and thiol ligand,
    (b) mixed liquor of heated at constant temperature step (a) obtains the gold nanoclusters；
    Preferably, the temperature of the heated at constant temperature is 40~120 DEG C, more preferably 50~100 DEG C, is most preferably 70 DEG C, and/or
    The time of the heated at constant temperature is 12~48h, is preferably 18~30h, is most preferably 24h.
  6. 6. prepared by the gold nanoclusters or preparation method according to claim 4 or 5 any one of claims 1 to 3 Gold nanoclusters prepare for antibacterial medicine or medical product in application；
    Preferably, the targeted bacterium of the antibacterial is multidrug resistance bacterium.
  7. 7. application according to claim 6, it is characterised in that the targeted bacterium of the antibacterial is Gram-negative bacteria, Preferably, the Gram-negative bacteria is selected from：Shigella dysenteriae, typhoid bacillus, Escherichia coli, proteus, Pseudomonas aeruginosa, one hundred days Cough bacillus, comma bacillus and diplococcus meningitidis.
  8. 8. application according to claim 6, it is characterised in that the targeted bacterium of the antibacterial is gram-positive bacteria, Preferably, the gram-positive bacteria is selected from：Staphylococcus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, corynebacterium diphtheriae and broken Cold bacillus.
  9. 9. prepared by the gold nanoclusters or preparation method according to claim 4 or 5 any one of claims 1 to 3 Gold nanoclusters be used to prevent and/or treat by Gram-negative bacteria and/or the microbial illness of Gram-positive preparing Application in medicine or medical product；
    Preferably, the illness is selected from following one or more：Infection of skin and subcutaneous tissue, wound infection, tympanitis, brain Film inflammation, peritonitis, enteritis, bronchitis, pneumonia, respiratory tract infection, urinary system infection contamination, septicemia and pyemia.
  10. 10. a kind of bactericidal composition, antibacterial combination product or antibiotic paint, it is characterised in that the bactericidal composition, antibacterial group Product or antibiotic paint are closed comprising the gold nanoclusters any one of claim 1 to 5 or according to claim 6 or 7 Preparation method prepare gold nanoclusters, the antibacterial combination product is preferably kit form.
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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107362370A (en) * 2016-05-13 2017-11-21 国家纳米科学中心 A kind of method based on gold nanoclusters joint NGF siRNA treatment cancers of pancreas
CN109091679A (en) * 2018-09-03 2018-12-28 国家纳米科学中心 Gold nano-material, preparation method and application
CN109986090A (en) * 2019-03-22 2019-07-09 华南理工大学 A kind of double ligand gold nanoparticle aqueous solutions and its preparation method and application
CN110787066A (en) * 2019-10-24 2020-02-14 深圳永昌和科技有限公司 Dental 3D printing antibacterial material and preparation method thereof
CN110935030A (en) * 2019-11-13 2020-03-31 南方科技大学 Gold nanocluster and preparation method and application thereof
CN111514308A (en) * 2020-03-10 2020-08-11 西南民族大学 PH-induced charge-inversion antibacterial gold nanorod and preparation method and application thereof
CN111658758A (en) * 2020-05-27 2020-09-15 华南理工大学 Antibacterial gold nanocluster and preparation method and application thereof
CN111906328A (en) * 2020-08-11 2020-11-10 苏州大学 A kind of177Lu-labeled gold nanocluster and preparation method and application thereof
CN111956808A (en) * 2020-07-02 2020-11-20 首都医科大学 Polypeptide-modified gold nanocluster, preparation method thereof and application thereof in tumor treatment
CN113318124A (en) * 2021-05-26 2021-08-31 徐州医科大学 Application of nanogold in preparation of medicine for treating shigella infectious enteritis and pharmaceutical preparation of nanogold
WO2022110911A1 (en) * 2020-11-27 2022-06-02 Shenzhen Profound View Pharmaceutical Technology Co., Ltd. Gold clusters, compositions, and methods for treatment of cerebral strokes
CN115025250A (en) * 2022-05-17 2022-09-09 南方科技大学 Gold nanocluster and preparation method and application thereof
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2226082A2 (en) * 2009-03-05 2010-09-08 Universität Duisburg-Essen Control of the toxicity of gold nanoparticles
CN101875132A (en) * 2010-05-31 2010-11-03 武汉大学 Method for bionically preparing water-soluble gold nanoclusters
CN102188383A (en) * 2010-03-05 2011-09-21 国家纳米科学中心 Amiopyrimidine-modified gold nano particles and preparation method and use thereof
CN103070691A (en) * 2012-11-09 2013-05-01 哈尔滨师范大学 Method for manifesting latent fingerprints on basis of fluorescent gold nanoclusters
CN104749151A (en) * 2015-04-08 2015-07-01 东南大学 Application of glutathione-based stable gold nano cluster particles to detection of sulfhydryl compound
CN105597159A (en) * 2016-01-15 2016-05-25 国家纳米科学中心 Gold nano-particle based antibacterial product and preparation method and application thereof

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2226082A2 (en) * 2009-03-05 2010-09-08 Universität Duisburg-Essen Control of the toxicity of gold nanoparticles
CN102188383A (en) * 2010-03-05 2011-09-21 国家纳米科学中心 Amiopyrimidine-modified gold nano particles and preparation method and use thereof
CN101875132A (en) * 2010-05-31 2010-11-03 武汉大学 Method for bionically preparing water-soluble gold nanoclusters
CN103070691A (en) * 2012-11-09 2013-05-01 哈尔滨师范大学 Method for manifesting latent fingerprints on basis of fluorescent gold nanoclusters
CN104749151A (en) * 2015-04-08 2015-07-01 东南大学 Application of glutathione-based stable gold nano cluster particles to detection of sulfhydryl compound
CN105597159A (en) * 2016-01-15 2016-05-25 国家纳米科学中心 Gold nano-particle based antibacterial product and preparation method and application thereof

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Publication number Priority date Publication date Assignee Title
CN107362370A (en) * 2016-05-13 2017-11-21 国家纳米科学中心 A kind of method based on gold nanoclusters joint NGF siRNA treatment cancers of pancreas
CN107362370B (en) * 2016-05-13 2022-07-26 国家纳米科学中心 Method for treating pancreatic cancer based on combination of gold nanoclusters and NGF siRNA
CN109091679A (en) * 2018-09-03 2018-12-28 国家纳米科学中心 Gold nano-material, preparation method and application
CN109091679B (en) * 2018-09-03 2021-11-19 国家纳米科学中心 Gold nano material, preparation method and application thereof
CN109986090B (en) * 2019-03-22 2021-03-30 华南理工大学 Double-ligand gold nanoparticle aqueous solution and preparation method and application thereof
CN109986090A (en) * 2019-03-22 2019-07-09 华南理工大学 A kind of double ligand gold nanoparticle aqueous solutions and its preparation method and application
CN110787066A (en) * 2019-10-24 2020-02-14 深圳永昌和科技有限公司 Dental 3D printing antibacterial material and preparation method thereof
CN110935030A (en) * 2019-11-13 2020-03-31 南方科技大学 Gold nanocluster and preparation method and application thereof
CN110935030B (en) * 2019-11-13 2023-01-10 南方科技大学 Gold nanocluster and preparation method and application thereof
CN111514308A (en) * 2020-03-10 2020-08-11 西南民族大学 PH-induced charge-inversion antibacterial gold nanorod and preparation method and application thereof
CN111514308B (en) * 2020-03-10 2023-02-17 西南民族大学 PH-induced charge-inversion antibacterial gold nanorod and preparation method and application thereof
CN111658758A (en) * 2020-05-27 2020-09-15 华南理工大学 Antibacterial gold nanocluster and preparation method and application thereof
CN111956808A (en) * 2020-07-02 2020-11-20 首都医科大学 Polypeptide-modified gold nanocluster, preparation method thereof and application thereof in tumor treatment
CN111906328A (en) * 2020-08-11 2020-11-10 苏州大学 A kind of177Lu-labeled gold nanocluster and preparation method and application thereof
WO2022110911A1 (en) * 2020-11-27 2022-06-02 Shenzhen Profound View Pharmaceutical Technology Co., Ltd. Gold clusters, compositions, and methods for treatment of cerebral strokes
CN113318124A (en) * 2021-05-26 2021-08-31 徐州医科大学 Application of nanogold in preparation of medicine for treating shigella infectious enteritis and pharmaceutical preparation of nanogold
CN115025250A (en) * 2022-05-17 2022-09-09 南方科技大学 Gold nanocluster and preparation method and application thereof
CN115025250B (en) * 2022-05-17 2024-01-16 南方科技大学 Gold nanocluster and preparation method and application thereof
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CN116019926B (en) * 2023-03-24 2023-06-23 潍坊科技学院 Photodynamic antibacterial agent and preparation method and application thereof

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