A method for synthesizing capsular polysaccharide and its antibiotic nanoparticles and their application

Abstract

The invention discloses a method for synthesizing a capsular polysaccharide and an antibiotic nanoparticle thereof and an application thereof. The capsular polysaccharide is obtained by ultrasonic alcohol precipitation from a fermentation culture broth of Lactobacillus plantarum with a strain number of LCC-605, and is named CPS-605. The method for synthesizing the capsular polysaccharide-antibiotic nanoparticles is as follows: CPS-605 is prepared into a 1-4 mg / mL aqueous solution, and its pH is adjusted to be greater than 10, sodium bromide and TEMPO reagent are dissolved in water, and after mixing with the prepared CPS-605 aqueous solution, 8.5 mL of sodium hypochlorite is added, and the mixture is reacted at 4°C and 100-1000 rpm for 30 min-1 h, and finally the oxidized CPS-605, EDC·HCl and NHS are dissolved in deionized water and reacted at room temperature and 100-1000 rpm for 1-3 h, and then amino antibiotics and / or polypeptide antibacterial substances are added thereto, and the mixture is reacted overnight at room temperature and 100-1000 rpm. The CPS-AM nanoparticles of the present invention exhibit good antibacterial effects on Gram-negative bacteria, have excellent biosafety and high-efficiency antibacterial properties, and can inhibit the growth of biofilms and remove pre-formed biofilms.

Description

Technical Field

[0001] The invention relates to a synthesis method and application of capsular polysaccharide and antibiotic nanoparticles thereof, belonging to the technical field of nanomaterials and nanomedicine. Background Art

[0002] At present, diseases caused by microbial infections have caused great harm to human health. And with the increase of microbial resistance, the prevention and treatment of related diseases has become increasingly difficult. Biofilm is a persistent source of microbial contamination that is difficult to eliminate, and may reduce the sensitivity of bacteria to certain antibiotics and other drugs, making related diseases difficult to cure. Antibiotics are often used to kill or inhibit various pathogenic microorganisms, but the use of antibiotics may lead to the widespread emergence of drug-resistant bacteria (Ciofu, Rojo-Molinero, Macia, & Oliver, 2017). Therefore, reducing the use of antibiotics and reducing the proliferation of bacteria at the site of infection is very important for the treatment of infectious diseases.

[0003] Among these antibiotics, aminoglycoside antibiotics have attracted widespread attention for their broad-spectrum activity, rapid antibacterial effect, and good chemical and pharmacokinetic properties. Amikacin (AM) is one of the most commonly used aminoglycoside antibiotics and is suitable for combating infections caused by Gram-negative bacteria (Meyer, 1975). It has been widely used to treat various infections that are resistant to other antibiotics. However, in order to survive and reproduce, bacteria will adjust their own metabolism to adapt to environmental conditions, thereby developing drug resistance. In addition, the effect of using antibiotics alone to eliminate biofilms is often poor, and surgical intervention is usually required. The development of new antibiotic drugs can no longer meet current needs, and there is an urgent need to develop some strategies to reduce the working concentration of antibiotics and combat biofilms.

[0004] With the booming development of nanotechnology, the combination of antimicrobial agents and nanoparticles can prevent the development of bacterial resistance. Some liposomes and polymer nanoparticles have been developed to reduce the dosage of antibiotics and can be used to inhibit the formation of biofilms (Abass, Afroz, Sourabh, Javed, & Ameer, 2018). Although nanomaterials can reduce the working concentration of antibiotics, the particle size of the antibiotic carriers currently developed is generally large (Fatima, Iqbal, Panda, Samim, Talegaonkar, & Ahmad, 2018). Some metal nanoparticles are also toxic to microorganisms themselves and human cells, and have poor biocompatibility (Liao, Li, & Tjong, 2019). As a nanomaterial, microbial capsular polysaccharides have a smaller particle size and are derived from microorganisms. They are safe, non-toxic and harmless to the human body. Therefore, they are a promising nanoparticle. Summary of the invention

[0005] In order to solve the above technical problems, the present invention cross-links amikacin (AM) and capsular polysaccharides together through covalent cross-linking to obtain a covalent cross-linked product CPS-AM. CPS-AM nanoparticles have shown good antibacterial effects on Gram-negative bacteria, have excellent biosafety and high-efficiency antibacterial properties, and can inhibit the growth of biofilms and remove pre-formed biofilms. This solves the problems of some existing antibacterial materials such as high cytotoxicity, poor biosafety, poor antibacterial effects, and drug resistance caused by the use of high concentrations of antibiotics. This method is expected to be widely used in the development of new antibacterial agents that reduce the amount of antibiotics used. The specific technical scheme of the present invention is as follows:

[0006] A capsular polysaccharide is obtained by ultrasonic alcohol precipitation of the fermentation culture fluid of Lactobacillus plantarum with the strain number of LCC-605, and is named CPS-605.

[0007] A method for producing the above-mentioned capsular polysaccharide, wherein the fermentation temperature is 31°C and the time is 18 hours; the ultrasonic power of the ultrasonic alcohol precipitation is 40w, the time is 30min, and the interval time is 5s.

[0008] A method for synthesizing capsular polysaccharide-antibiotic nanoparticles comprises the following steps:

[0009] (1) Prepare CPS-605 into a 1-4 mg / mL aqueous solution and adjust its pH to > 10.

[0010] (2) Sodium bromide and TEMPO reagent were dissolved in water, mixed with the prepared CPS-605 aqueous solution, and then 8.5 mL of sodium hypochlorite was added. The mixture was reacted at 4°C and 100-1000 rpm for 30 min-1 h.

[0011] (3) The oxidized CPS-605, EDC·HCl, and NHS are dissolved in deionized water and reacted at room temperature and 100-1000 rpm for 1-3 hours, and then amino antibiotics and / or polypeptide antibacterial substances are added thereto and reacted at room temperature and 100-1000 rpm overnight.

[0012] Further: the amino antibiotic and / or polypeptide antibacterial substance is one or more of streptomycin, kanamycin, polymyxin B and bacteriocin.

[0013] Furthermore: the amino antibiotic and / or polypeptide antibacterial substance is amikacin.

[0014] Furthermore: the ratio of the TEMPO reagent to CPS-605 is 1:(1-5).

[0015] Furthermore: the ratio of the TEMPO reagent to CPS-605 is 1:4.

[0016] Furthermore: the mass ratio of the oxidized CPS-605 to amikacin is 1:(0.1-1).

[0017] Furthermore: the mass ratio of the oxidized CPS-605 to amikacin is 1:0.78.

[0018] An application of capsular polysaccharide-antibiotic nanoparticles, wherein the capsular polysaccharide-antibiotic nanoparticles synthesized by any of the above methods are applied to antibacterial and anti-biofilm aspects.

[0019] Beneficial effects:

[0020] 1. The capsular polysaccharide obtained by the present invention is derived from microorganisms, which have a fast growth cycle, cheap and readily available raw materials, high product yield, and production is not restricted by natural conditions such as geography, climate, and season.

[0021] 2. The capsular polysaccharide obtained by the present invention is naturally produced without any chemical synthesis, the preparation process is simple, and the potential residue of processing aids in the chemical synthesis process is avoided. Moreover, its main component, polysaccharide, is safe and non-toxic and harmless to the human body.

[0022] 3. CPS-AM nanoparticles have better antibacterial effect than free AM. The concentrations of CPS-AM nanoparticles that kill 100% of Escherichia coli and Pseudomonas aeruginosa are 100 μg / mL and 30 μg / mL, respectively, which are much lower than the corresponding free AM bactericidal concentrations.

[0023] 4. CPS-AM nanoparticles can inhibit Escherichia coli biofilm and have a significant clearing effect on mature Escherichia coli biofilm.

[0024] 5. CPS-AM has low cytotoxicity, short reaction time, and room temperature. Therefore, this method is expected to be widely used in the green synthesis of antibacterial nanoparticles. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 This is a schematic diagram of the capsular polysaccharide produced by Lactobacillus plantarum LCC-605 under an electron microscope in the embodiment.

[0026] Figure 2 This is a schematic diagram of the statistical results of the particle size of the capsular polysaccharide produced by Lactobacillus plantarum LCC-605 in the example.

[0027] Figure 3 Schematic diagram of CPS-AM nanoparticles prepared in the example under electron microscope,

[0028] Figure 4 Schematic diagram of the particle size statistics of CPS-AM nanoparticles prepared in the examples,

[0029] Figure 5 It is a schematic diagram of the potential results of CPS and CPS-AM in the embodiment,

[0030] Figure 6 This is a schematic diagram of the CPS-AM anti-E. coli experimental results in the example,

[0031] Figure 7 This is a schematic diagram of the experimental results of CPS-AM against Pseudomonas aeruginosa in the embodiment,

[0032] Figure 8 This is a schematic diagram of the experimental results of CPS-AM against Escherichia coli in a short period of time in the embodiment.

[0033] Fig. 9 This is a schematic diagram of the experimental results of CPS-AM against Pseudomonas aeruginosa in a short period of time in the embodiment.

[0034] Fig.10 This is a schematic diagram of the destruction of Escherichia coli after being acted upon by CPS-AM in the embodiment.

[0035] Fig.11 This is a schematic diagram of the destruction of Pseudomonas aeruginosa after being acted upon by CPS-AM in the embodiment.

[0036] Fig. 12A This is a 3D image of the E. coli biofilm treated with CPS-AM nanoparticles in the embodiment after 24h of laser confocal observation. The excitation wavelength is 488nm and the CPS-AM used is 200μg / mL.

[0037] Fig. 12B This is a 3D image of the E. coli biofilm treated with CPS-AM nanoparticles in the embodiment, cultured for 24 hours by laser confocal observation. The excitation wavelength is 488 nm, and the CPS-AM used is 0 μg / mL.

[0038] Fig.13 This is the scanning electron microscope image of the Escherichia coli biofilm grown for 24 hours and treated with 0 μg / mL CPS-AM nanoparticles for 24 hours in the example.

[0039] Fig.14 This is a scanning electron microscope image of the Escherichia coli biofilm grown for 24 hours and treated with 200 μg / mL CPS-AM nanoparticles for 24 hours in the example.

[0040] Fig.15A This is a 3D image of the E. coli biofilm grown for 24 hours and treated with CPS-AM nanoparticles for 24 hours by laser confocal observation. The CPS-AM used is 0 μg / mL.

[0041] Figure 15A-1 for Fig.15A Grayscale image of

[0042] Fig. 15B This is a 3D image of the E. coli biofilm grown for 24 hours and treated with CPS-AM nanoparticles for 24 hours by laser confocal observation. The CPS-AM used is 300 μg / mL.

[0043] Figure 15B-1 for Fig. 15B Grayscale image of

[0044] Fig.16 This is a schematic diagram of evaluating the toxic activity of CPS-AM nanoparticles prepared in the examples on animal cells.

[0045] Fig.17 Schematic diagram of the hemolytic experiment of CPS-AM nanoparticles prepared in the example. DETAILED DESCRIPTION

[0046] The present invention is further explained below in conjunction with the accompanying drawings and specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention. After reading the present invention, various equivalent forms of modifications to the present invention by those skilled in the art all fall within the scope defined by the claims attached to this application.

[0047] Experimental pretreatment

[0048] Strain activation method: Escherichia coli and Pseudomonas aeruginosa strains stored in a -80°C refrigerator were inoculated into 10 mL LB broth medium at a 3% inoculation rate and cultured at 37°C for 12 hours to activate the strains.

[0049] Determination of viable count: The determination of viable count was carried out by dilution plating method, as follows: 0.1 mL of sample solution was pipetted into a sterile centrifuge tube and diluted with sterile saline to a dilution of 10 -1 , 10 -2 , 10 -3 , 10 -4 , 10 -5 , 10 -6 , 10 -7 , 10 -8 , 10 -9 , 10 -10 , 10 -11 , 10 -12 The dilution was selected as 10 -4 Up to 10 -12 Spread on LB medium, do three replicates for each dilution, and culture in a 31°C incubator for 24 hours before counting.

[0050] Example

[0051] Extraction of CPS-605

[0052] Capsular polysaccharide extraction was performed by alcohol precipitation, as follows: the fermentation broth fermented in liquid MRS or whey for 18 h was centrifuged (14000×g, 4°C, 30 min) to collect the bacterial cells, the obtained bacterial cells were washed twice with 0.85% NaCl, resuspended in 0.85% NaCl and subjected to ultrasonic treatment (40w, 4°C, 30min, interval 5s), centrifuged (15000×g, 4°C, 15min) to collect the supernatant, and then added to the collected supernatant. TCA (trichloroacetic acid) with a final concentration of 4% was added to the supernatant and placed in a 4°C refrigerator for overnight treatment. The protein was removed by centrifugation (14000×g, 4°C, 30min). Three volumes of anhydrous ethanol were added to the supernatant and placed in a 4°C refrigerator for alcohol precipitation overnight. The precipitate was collected by centrifugation (14000×g, 4°C, 30min). The precipitate was dialyzed with a 14000Da dialysis bag at 4°C for 72h and freeze-dried to obtain capsular polysaccharide (CPS-605).

[0053] Synthesis of CPS-AM nanoparticles

[0054] 20 mg of CPS-605 was dispersed in 5 mL of deionized water and the pH of the solution was adjusted to greater than 10 with 0.1 M NaOH. The CPS-605 dispersion was then mixed with 5 mg of TEMPO, 0.1 g of NaBr, and 8.5 mL of NaClO and stirred at room temperature for 1 h. The resulting solution was dialyzed with deionized water (MW = 3 kDa) for 24 h to remove residual small molecules, thereby obtaining oxidized CPS-605.

[0055] The oxidized CPS-605 obtained after dialysis was mixed with 1 mL of EDC-HCl solution (56 μg / mL), stirred at room temperature for 10 min, and 1 mL of NHS solution (34 μg / mL) was added and incubated at room temperature for 1 h at 90 rpm. 15.6 mg of amikacin was added, and the mixture was magnetically stirred at room temperature for 24 h. The resulting solution was dialyzed with deionized water (MW = 3 kDa) for 24 h to remove residual amikacin, thereby obtaining capsular polysaccharide-amikacin nanoparticles.

[0056] The following is a performance test experiment on the CPS-605 and CPS-AM nanoparticles synthesized in this example.

[0057] Morphological observation of CPS-605 and CPS-AM

[0058] The CPS-605 and CPS-AM nanoparticles obtained in the above examples were dispersed in deionized water to prepare a 1 mg / mL dispersion, and 10 μL of the dispersion was dropped on a silicon wafer for field emission scanning electron microscopy observation. The formed CPS-605 and CPS-AM nanoparticles were spherical structures, such as Figure 1 and Figure 3 At the same time, the particle size distribution statistics were performed, and the results showed that the particle size of the capsule polysaccharide particles was about 65.7nm, and the particle size of the capsule polysaccharide-amikacin nanoparticles was about 49.9nm. Figure 2 and Figure 4 shown.

[0059] CPS, CPS-AM charged

[0060] The Zeta potential of CPS and CPS-AM nanoparticles was analyzed using a Zetasizer 3000 (Malvern Instruments, Nano ZS, United Kingdom). Figure 5 shown.

[0061] Minimum inhibitory concentration (MIC) of CPS-AM

[0062] CPS-AM was diluted to a suitable concentration range with LB broth, and the bacterial culture was diluted in LB medium to an optical density (OD) of 600 nm. 600 ) was 0.05, and an equal amount of bacterial suspension was added to each centrifuge tube. The centrifuge tubes were placed in a shaking incubator at 37°C for 24 h, and the OD of the suspension in each centrifuge tube was measured. 600 The results showed that the minimum inhibitory concentration of CPS-AM nanoparticles against Escherichia coli was 100 μg / mL and the minimum inhibitory concentration against Pseudomonas aeruginosa was 30 μg / mL.

[0063] Antibacterial properties of CPS-AM

[0064] Dilute the activated bacteria to OD 600 The results showed that CPS-AM exhibited excellent antibacterial activity and could reduce the dosage of amikacin. Figure 6 (The dotted circle indicates that no bacteria survived) As shown in Figure 1, 8.8 μg / mL of CPS-AM can kill 100% of E. coli, but for amikacin alone, E. coli still survived at a concentration of 26.4 μg / mL. The results for Pseudomonas aeruginosa are as follows Figure 7 As shown, only 2.8 μg / mL of CPS-AM was needed to kill 99% of the bacteria, which was much lower than using amikacin alone.

[0065] Rapid sterilization capability of CPS-AM

[0066] Dilute the activated bacteria to OD 600The CPS-AM at different concentrations was added to the bacterial suspension and the number of viable bacteria was measured after culturing at 37°C for 0, 10, 20, 30 and 60 min. CPS-AM showed significant rapid bactericidal activity. Figure 8 As shown. When E. coli was exposed to 300 μg / mL CPS-AM for 10 minutes, 99.9% of the bacteria were killed. When the time reached 30 minutes and 60 minutes, only 100 μg / mL CPS-AM could completely inhibit all E. coli. CPS-AM also has rapid bactericidal activity against Pseudomonas aeruginosa, such as Fig. 9 As shown, 100 μg / mL of CPS-AM can kill more than 99% of Pseudomonas aeruginosa in 20 minutes. In short, CPS-AM can kill 99.99% of Escherichia coli and Pseudomonas aeruginosa within 10 minutes after treatment.

[0067] Inhibitory ability of CPS-AM on biofilm

[0068] Dilute the activated E. coli in LB broth to an OD of 600 The concentration of CPS-AM was 0.1. 100 μL of bacterial solution was transferred to a sterile glass culture dish, and different concentrations of CPS-AM (0, 200 μg / mL) were added. After 72 hours of static culture at 37°C, samples were taken. After pouring out the broth from the culture dish, it was gently rinsed 3 times with sterile saline to remove unattached cells and culture medium components. The washed biofilm was stained with the Live / Dead BacLight bacterial viability kit. The culture dish was incubated at 37°C in the dark for 20 minutes. Subsequently, it was observed with a laser confocal scanning microscope.

[0069] The results are as follows Fig. 12A and 12B As shown, CPS-AM has the ability to inhibit the formation of biofilm. The biomass of E. coli biofilm treated with 200 μg / mL CPS-AM was significantly reduced. Fig. 12A and 12B In the figure, the units on the x, y, and z axes are all μm. The biofilm grown in 200 μg / mL CPS-AM for 72 hours is only about 7 μm. Fig. 12A As shown; under the same conditions, the biofilm grown in the medium without adding CPS-AM was 20 μm, as shown Fig. 12B In addition, there are obvious dead cells in the biofilm after CPS-AM treatment, as shown in Fig.10 and Fig.11 shown.

[0070] Removal ability of CPS-AM on biofilm

[0071] Dilute the activated E. coli in LB broth to an OD of600 The concentration of 1 μg / mL CPS-AMNPS was 0.1. 100 μL of bacterial solution was transferred to a sterile glass culture dish and incubated at 37°C for 24 h. Subsequently, the culture medium was removed and 100 μL of CPS-AMNPS (0, 300 μg / mL) CPS-AM NPs of different concentrations were added and incubated at 37°C for 24 h. The biofilm morphology was observed by laser confocal scanning microscopy images as described above. Scanning electron microscope images of the biofilm were taken 24 h after treatment. Fig.13 As shown in Figure 2, a dense biofilm can be observed in the sample without the addition of CPS-AM, while a dense biofilm can be observed in the sample with the addition of 300 μg / mL CPS-AM. Fig.14 As shown in the figure, the biofilm gradually loosened and decreased after treatment. Although the destruction of bacterial cells could not be clearly observed, it could be found that the bacteria were in a free state and could not form a dense biofilm. Fig.15A The confocal images showed that the untreated biofilm was almost entirely green, while the biofilm treated with 300 μg / mL CPS-AM was Fig. 15B As shown, the death of biofilm gradually increased after treatment.

[0072] CPS-AM NPS safety evaluation

[0073] To evaluate the biosafety of CPS-AM, CPS-AM nanoparticles were subjected to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and hemolysis assay as follows.

[0074] The MTT assay method is as follows: HP cells are plated at 1×10 5 The cells were seeded in a 96-well plate at a density of 10 cells / well and incubated at 37°C and 5% CO2 for 24 hours. After that, the culture medium was replaced with fresh DMEM medium containing different concentrations of CPS-AM and cultured for another 24 hours under the same conditions. 10 μL of MTT solution (5 mg / mL) was added to each well. After another 4 hours of incubation, the solution was discarded and 150 μL of DMSO was added. The absorbance at 570 nm was recorded using a microplate reader.

[0075] The hemolysis assay was performed by centrifuging mouse whole blood at 2500 rpm for 5 min, washing three times to remove residual serum, and then suspending in PBS buffer. The collected erythrocytes were treated with different concentrations of CPS-AM. After incubation at 37°C for 1 h, the mixture was centrifuged at 4000 rpm for 5 min. Erythrocytes incubated with PBS and ultrapure water were used as negative and positive controls, respectively. The hemolysis percentage was calculated using the following equation:

[0076] Hemolysis % = (sample absorbance negative control absorbance) / (positive control absorbance negative control absorbance) × 100%

[0077] The results are as follows Fig.16 As shown in Figure 2, CPS-AM has good biocompatibility. CPS-AM has almost no cytotoxicity to AT II cells at 300 μg / mL, which is higher than its working concentration for Escherichia coli (200 μg / mL) and Pseudomonas aeruginosa (100 μg / mL). The hemolytic activity of CPS-AM on red blood cells is also negligible. Fig.17 As shown, almost no hemolysis was observed after treatment with 300 μg / mL CPS-AM.

[0078] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

[0079] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A capsular polysaccharide, characterized in that The product is obtained by ultrasonic alcohol precipitation from the fermentation culture broth of Lactobacillus plantarum with the strain number LCC-605, and is named CPS-605; the manufacturing method of the CPS-605 is as follows: the fermentation broth fermented in liquid MRS or whey for 18 hours is centrifuged at 14000g and 4°C for 30 min to collect the bacterial cells, the obtained bacterial cells are washed twice with 0.85% NaCl, resuspended in 0.85% NaCl and subjected to 40 w, 4°C, 5 s interval ultrasonic treatment for 30 min, centrifuged at 15000g and 4°C for 15 min to collect the supernatant, trichloroacetic acid with a final concentration of 4% is added to the collected supernatant, and the supernatant is placed in a refrigerator at 4°C for overnight treatment, centrifuged at 14000g and 4°C for 30 min to remove protein, 3 times the volume of anhydrous ethanol is added to the supernatant, and the supernatant is placed in a refrigerator at 4°C for alcohol precipitation overnight, centrifuged at 14000g and 4°C for 30 min to collect the precipitate, and the precipitate is dialysis bag with 14000 Da at 4 The solution was dialyzed at 400 °C for 72 h and freeze-dried to obtain capsular polysaccharide CPS-605.

2. The method for producing capsular polysaccharide according to claim 1, characterized in that: The fermentation temperature was 31°C.

3. A method for synthesizing capsular polysaccharide-antibiotic nanoparticles, characterized in that: The following steps are involved: (1) The CPS-605 in claim 1 is prepared into a 1-4 mg / mL aqueous solution and its pH is adjusted to > 10. (2) Dissolve sodium bromide and TEMPO reagent in water, mix with the prepared CPS-605 aqueous solution, add 8.5 mL of sodium hypochlorite, and react at 4°C and 100-1000 rpm for 30 min-1 h. (3) The oxidized CPS-605, EDC·HCl, and NHS are dissolved in deionized water and reacted at room temperature and 100-1000 rpm for 1-3 hours, and then amino antibiotics and / or polypeptide antibacterial substances are added thereto and reacted at room temperature and 100-1000 rpm overnight. The ratio of TEMPO reagent to CPS-605 in step (2) is 1:(1-5).

4. The method for synthesizing capsular polysaccharide-antibiotic nanoparticles according to claim 3, characterized in that: The amino antibiotic and / or polypeptide antibacterial substance is one or more of streptomycin, kanamycin, polymyxin B and bacteriocin.

5. The method for synthesizing capsular polysaccharide-antibiotic nanoparticles according to claim 3, characterized in that: The amino antibiotic and / or polypeptide antibacterial substance is amikacin, and the mass ratio of oxidized CPS-605 to amikacin is 1:(0.1-1).

6. The method for synthesizing capsular polysaccharide-antibiotic nanoparticles according to claim 3, characterized in that: The ratio of the TEMPO reagent to CPS-605 is 1:

4.

7. The method for synthesizing capsular polysaccharide-antibiotic nanoparticles according to claim 5, characterized in that: The mass ratio of the oxidized CPS-605 to amikacin is 1:0.

78.

8. An application of capsular polysaccharide-antibiotic nanoparticles, characterized in that: The capsule polysaccharide-antibiotic nanoparticles synthesized by any of the methods of claims 3-7 are applied to antibacterial and anti-biofilm aspects.

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