Preparation method and application of mesoporous polydopamine nano-antibacterial agent loaded with organic arsenic agent
By loading nitric oxide donors and the organic arsenic fungicide roxarsone onto mesoporous polydopamine nanoparticles and utilizing the synergistic effect of photothermal conversion and nitric oxide, the problem of reduced drug resistance of organic arsenic fungicides was solved, achieving efficient killing of drug-resistant bacteria and precise control of drug delivery.
Patent Information
- Application Number
- CN202211005810.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-08-22
- Publication Date
- 2025-09-23
- Estimated Expiration
- 2042-08-22
AI Technical Summary
The antibacterial effects of existing organic arsenic fungicides are weakened due to bacterial resistance, and the development cycle of new drugs is long and the cost is high, making it difficult to effectively solve the problem of drug-resistant bacteria in agriculture and livestock farming.
Mesoporous polydopamine nanoparticles are used as carriers to load nitric oxide donor groups through nitrosation reaction, and to adsorb the organic arsenic fungicide roxarsone. The synergistic effect of photothermal conversion and nitric oxide is utilized to achieve precise and controllable drug release to enhance the antibacterial effect.
It achieves efficient and controllable killing effects on drug-resistant bacteria, simplifies the preparation process, shortens the R&D cycle, and maintains good blood compatibility at low concentrations.
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Figure CN115414495B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of pharmaceutical chemistry and material technology, and particularly relates to a preparation method and application of a mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent. Background Art
[0002] Arsenic-containing fungicides are organic synthetic fungicides containing arsenic (As) in their chemical structure. Arsenic-containing drugs are widely used in agriculture and livestock breeding, such as the most common roxarsone (ROX, As 5+ However, the abuse of chemical antimicrobial agents has led to the widespread emergence of drug-resistant bacteria, which has greatly weakened the effectiveness of traditional antimicrobial agents, including organoarsenic fungicides, and has had a serious impact on agriculture and livestock breeding.
[0003] To improve antimicrobial efficacy, increasing the dosage of organoarsenic fungicides is often used. However, this approach not only causes toxic pollution to the ecological environment and living organisms, but can also further increase the resistance of drug-resistant bacteria, creating a vicious cycle. Furthermore, researchers are also working to develop new antimicrobial drugs for use in agriculture and livestock farming. However, the development cycle and cost are high, and the effectiveness of these drugs is uncertain, making them a poor solution to the urgent problem.
[0004] In view of this, it is urgent to explore a strategy to improve antibacterial efficiency and reduce the occurrence of drug-resistant bacteria. Summary of the Invention
[0005] The purpose of the present invention is to solve the problem that the current organic arsenic fungicides cannot exert their best antibacterial effect due to bacterial resistance, and to provide a preparation method and application of a mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent.
[0006] The concept of the present invention:
[0007] Considering the current difficulty in developing new drugs, in order to solve the urgent problem, the research team of this invention intends to adopt the approach of "new uses for old drugs" and make full use of existing organic arsenic fungicides.
[0008] How to improve the antibacterial effect of current organic arsenic fungicides on drug-resistant bacteria? Researchers first need to improve the sensitivity of drug-resistant bacteria to organic arsenic fungicides. Here, researchers use nitric oxide. Nitric oxide (NO) is a gas signal molecule in living organisms that can increase the sensitivity of drug-resistant bacteria to antibacterial drugs, thereby enhancing the efficacy of antibacterial agents. However, how to combine the NO donor group with the organic arsenic fungicide is another problem encountered by researchers in the improvement process. Here, researchers creatively use intermediate carriers to integrate and transport drugs. Nano drug carriers are not only convenient to deliver but also can prolong the drug action time. In summary, the present invention sets out to utilize the synergistic effect of the nano drug delivery system and the photothermal controlled release effect to achieve high efficiency and high utilization rate of organic arsenic fungicides.
[0009] Mesoporous polydopamine nanoparticles (mPDA), as a photothermal agent, can not only effectively convert near-infrared light (NIR) into localized high temperatures, destroying bacterial structures to kill pathogens, but also their mesopores and surfaces can be used to adsorb and transport drugs. Therefore, using mesoporous polydopamine nanoparticles as an intermediate carrier to integrate NO donors and organoarsenic fungicides to prepare organoarsenic nanoantimicrobial agents with photothermal and NO enhancement is a feasible solution. At the same time, photothermal conversion can also promote the release of NO and drugs, thereby controlling the duration and location of drug action, with significant effects.
[0010] To achieve the above objectives, the technical solutions provided by the present invention are:
[0011] A mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent is characterized in that: the actual particle size of the nano-antibacterial agent is 20 to 200 nm, the carrier is mesoporous polydopamine nanoparticles surface-modified with nitric oxide donor groups, and the organic arsenic fungicide is adsorbed in the mesopores and on the surface of the carrier;
[0012] The nitric oxide donor group is loaded on the secondary amine active site of the mesoporous polydopamine nanoparticles through a nitrosation reaction, thereby modifying the mesoporous polydopamine nanoparticles;
[0013] When the nano antibacterial agent is irradiated with near-infrared light, the mesoporous polydopamine nanoparticles can promote the release of nitric oxide (NO) and organic arsenic fungicides while performing photothermal antibacterial activities. That is, the nanoparticles can achieve the release of nitric oxide (NO) and organic arsenic fungicides while performing photothermal antibacterial activities, thereby achieving a synergistic chemical-photothermal therapy that can precisely and controllably kill drug-resistant bacteria.
[0014] Furthermore, the organic arsenic fungicide is roxarsone ROX.
[0015] The present invention also provides a method for preparing the above-mentioned mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent, which is characterized by comprising the following steps:
[0016] 1) Preparation of modified mesoporous polydopamine nanoparticles (mPDA@NO nanoparticles)
[0017] By loading nitric oxide donor groups onto the secondary amine active sites of mesoporous polydopamine nanoparticles (mPDA nanoparticles) with a particle size of 20-200 nm through a nitrosation reaction, modified mesoporous polydopamine nanoparticles with nitric oxide release function, namely mPDA@NO nanoparticles. Nanoparticles below 200 nm ensure that the antimicrobial agent is endocytosed by cells to be effective.
[0018] 2) Preparation of nano antibacterial agents
[0019] A large amount of organic arsenic fungicide is adsorbed in the mesopores and on the surface of the modified mesoporous polydopamine nanoparticles obtained in step 1), thereby obtaining a nano antibacterial agent that can simultaneously release nitric oxide and the organic arsenic fungicide under near-infrared light irradiation.
[0020] Furthermore, step 1) is specifically as follows:
[0021] 1.1) ultrasonically dispersing mesoporous polydopamine nanoparticles having a particle size of 20-200 nm in an aqueous solution of sodium nitrite to obtain a mixture;
[0022] 1.2) Add the mixture obtained in step 1.1) dropwise to sulfuric acid in an ice bath (manually and slowly adding dropwise is sufficient), stir evenly, and place in a sealed container for reaction. After the reaction is complete, centrifuge to obtain the product;
[0023] 1.3) Washing the product obtained in step 1.2) with water and acetone to ensure that NaNO2 is completely removed (to test whether NaNO2 is completely removed, the supernatant after centrifugation can be taken and tested using the Griess method; if there is no absorption peak at 540 nm, it means that NaNO2 is completely removed), thereby obtaining modified mesoporous polydopamine nanoparticles with nitric oxide release function.
[0024] Furthermore, step 2) is specifically as follows:
[0025] The modified mesoporous polydopamine nanoparticles obtained in step 1) are dispersed in an organic arsenic fungicide solution, stirred evenly to allow the organic arsenic fungicide to adsorb on the mesopores and surface of the nanoparticles, and centrifuged to obtain a mesoporous polydopamine nanoantibacterial agent loaded with organic arsenic.
[0026] Furthermore, the preparation method of mesoporous polydopamine nanoparticles with a particle size of 20-200 nm in step 1) is as follows:
[0027] S1. Dissolve the emulsifier triblock copolymer F127 (poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)) and 1,3,5-trimethylbenzene (TMB) in a mixture of water and ethanol, stir until the emulsifier is evenly dispersed, and add tris(hydroxymethyl)aminomethane (TRIS) solution to adjust the pH of the mixture to 7-8, i.e., weakly alkaline.
[0028] S2 adds dopamine hydrochloride to the mixed solution obtained in S1, stirs and reacts, and after the reaction is complete, centrifuges and collects the nanoparticle product;
[0029] S3 uses a mixture of ethanol and acetone as an extractant to ultrasonically treat the nanoparticle product obtained in S2 to remove residual triblock copolymer F127 and TMB; repeat the washing process multiple times, and collect by centrifugation to obtain mesoporous polydopamine nanoparticles (mPDA).
[0030] The above-mentioned mesoporous polydopamine nanoparticles with a particle size of 20-200 nm are prepared by forming emulsion droplets on the water / 1,3,5-trimethylbenzene TMB interface through organic-organic self-assembly and π-π stacking interactions, and then directionally co-assembled.
[0031] Furthermore, the particle size of mesoporous polydopamine nanoparticles is affected by the reaction time, and the pore size is affected by the concentration of emulsifier F127 and TMB. To obtain nanoparticles with uniform size and appropriate pore size, in S1, the mass ratio of F127 to TMB was 1:1, and the concentration was adjusted to 0.64% (w / v) with water and ethanol, and the volume ratio of water to ethanol was 13:12. The emulsifier was evenly dispersed after stirring for half an hour.
[0032] In S2, the weight ratio of dopamine hydrochloride to the total weight of F127 and TMB was 1:13.3; the reaction was stirred for 24 hours, and the centrifugation speed was 9000 rpm for 15 minutes;
[0033] In S3, the volume ratio of ethanol to acetone is 2:1; the washing process is repeated 3 times.
[0034] Furthermore, in step 1.1), the mass concentration of the aqueous solution of sodium nitrite is 2.4% (w / v);
[0035] The mass ratio of mesoporous polydopamine nanoparticles to sodium nitrite is 1:5-10;
[0036] In step 1.2), the volume ratio of sulfuric acid to the mixture in step 1.1) is 6:1 to 5:1, and the molar concentration of sulfuric acid is 3M;
[0037] The reaction is carried out for 7-10 hours (preferably 8 hours), the centrifugal speed is 11000 rpm, and the centrifugal time is 25-35 minutes (preferably 30 minutes).
[0038] Furthermore, in step 2), the organic arsenic fungicide solution is a roxarsone solution, and its mass concentration is 0.1-0.8 mg / mL;
[0039] The mass ratio of modified mesoporous polydopamine nanoparticles to roxarsone solution is 1:0.5-4, which can achieve an adsorption standard of 130-580 μg / mg.
[0040] Stir evenly for 22 to 24 hours, preferably 24 hours.
[0041] The present invention also provides the use of the above-mentioned mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent in killing drug-resistant bacteria.
[0042] Mechanism of the present invention:
[0043] To create a highly effective and controllable antimicrobial agent for killing drug-resistant bacteria, researchers first leveraged the ability of NO donors to release antimicrobial NO upon heating. This NO donor was then loaded onto the secondary amine active sites of mesoporous polydopamine nanoparticles with photothermal conversion capabilities via a nitrosation reaction, yielding modified mPDA@NO nanoparticles. Using the modified mPDA@NO nanoparticles as carriers, they then adsorbed a large amount of an organic arsenic fungicide (such as ROX) into the nanopores and surfaces of the nanocarriers, creating a mesoporous polydopamine nanoantimicrobial agent loaded with both NO and the organic arsenic fungicide. Upon reaching a specific location (such as the site of bacterial infection) and under near-infrared (NIR) irradiation, the nanoparticles not only rapidly heat to exert their antimicrobial effect but also promote the release of the organic arsenic fungicide and NO. Through the synergistic effects of photothermal antibacterial therapy, NO-mediated antibacterial therapy, and medicinal chemical antibacterial therapy, the nanoparticles achieve precise controlled release and synergistic, highly effective killing of drug-resistant bacteria. That is, mesoporous polydopamine nanoparticles modified with NO donors are used as drug delivery carriers to achieve high utilization of organic arsenic fungicides (such as ROX). When PDA is irradiated by NIR at the location where antibacterial effect is required, it converts light into heat for sterilization (photothermal antibacterial) while promoting the release of NO and organic arsenic drugs for sterilization (chemical antibacterial), thus achieving precise and controllable photothermal-chemical synergistic and efficient sterilization.
[0044] The advantages of the present invention are:
[0045] 1. This invention aims to repurpose an old drug for a new purpose, designing and synthesizing a mesoporous polydopamine nanoantibacterial agent loaded with an organic arsenic agent. The preparation method is simple and easy to operate, significantly shortening the R&D cycle and ensuring a certain degree of bactericidal efficacy. By surface-modifying mPDA nanoparticles, mPDA@NO nanoparticles loaded with an NO donor were prepared. These nanoparticles were then used as drug carriers to adsorb the organic arsenic bactericide, yielding a nanoparticle antibacterial agent. Microscopic morphology analysis of the entire nanoparticle antibacterial agent confirmed that the prepared nanoparticles had a uniformly distributed true particle size (20-200 nm), which is within the range of cellular endocytosis. In addition, photothermal controlled release testing revealed that under NIR irradiation, the release amount and release rate of NO and the organic arsenic bactericide were significantly increased, demonstrating a significant photothermal conversion controlled release effect. Upon reaching the infection site, the particles were irradiated by NIR to release large amounts of drug and gas for efficient bactericidal efficacy, resulting in precise controllability. This invention can be applied to nanodrug delivery systems in fields related to combating drug-resistant bacterial infections.
[0046] 2. The nanoparticles prepared by the present invention have uniform particle size distribution, controllable morphology, and good photothermal conversion performance. The present invention studies the performance and effect of photothermal conversion controlled release of modified mPDA nanoparticles, and compares the antibacterial performance and hemolysis rate of mPDA nanoparticles modified with different loads. Experiments have confirmed that the prepared mPDA@NO-ROX nanoparticles use their synergistic chemical-photothermal thermal function after illumination to show the best antibacterial effect against drug-resistant bacteria. Therefore, the antibacterial drug can be delivered to the infection site and then NIR can be used to achieve precise control of the bactericidal effect. In addition, when the concentration used is lower than 1 mg / ml, the mPDA@NO-ROX nanoparticles can be guaranteed to have good blood compatibility. Therefore, the development of mesoporous polydopamine nanodrug delivery systems loaded with organic arsenic agents has potential application prospects in the field of combating drug-resistant bacterial infections. BRIEF DESCRIPTION OF THE DRAWINGS
[0047] Figure 1 Schematic diagram of the preparation of mPDA@NO-ROX nanoparticles and the mechanism of photothermal controlled release;
[0048] Figure 2 Scanning electron microscopy (SEM) images of mPDA nanoparticles before and after modification;
[0049] Figure 3 is the nitrogen adsorption-desorption curve of mPDA nanoparticles;
[0050] Figure 4 is the hydrated particle size distribution diagram;
[0051] Figure 5X-ray photoelectron spectroscopy (XPS) of mPDA, mPDA@NO, and mPDA@NO-ROX nanoparticles;
[0052] Figure 6 Ultraviolet absorption spectra (UV-vis) of ROX, mPDA, mPDA@NO, and mPDA@NO-ROX nanoparticles;
[0053] Figure 7 The effect of the weight ratio of mPDA and ROX on the adsorption capacity and loading efficiency of ROX;
[0054] Figure 8 is the photothermal release efficiency of ROX from mPDA-ROX nanoparticles;
[0055] Figure 9 The performance of mPDA@NO nanoparticles in controlling NO release through photothermal conversion;
[0056] Figure 10 Hemolysis rates of mPDA, mPDA@NO, and mPDA@NO-ROX nanoparticles at different mass concentrations (a) and photos of red blood cell suspensions incubated with Triton X-100 (b);
[0057] Figure 11 Antibacterial properties of differently modified mPDA nanoparticles against drug-resistant Escherichia coli (a) and drug-resistant Staphylococcus aureus (b) in the presence and absence of NIR. DETAILED DESCRIPTION
[0058] The present invention will be described in further detail below with reference to the accompanying drawings and specific embodiments:
[0059] Example 1
[0060] A method for preparing a mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent comprises the following steps:
[0061] 1) Preparation of mPDA nanoparticles
[0062] 1.1) Dissolve 0.4 g of F127 and 0.4 g of TMB in a mixture of water (65 mL) and ethanol (60 mL). Stir for half an hour until the emulsifier is evenly dispersed. Add Tris buffer (90 mg of Tris dissolved in 10 mL of water) to adjust the solution to a slightly alkaline pH of 7-8.
[0063] 1.2) Add 60 mg of dopamine hydrochloride to the mixed solution obtained in step 1.1). After stirring for 24 hours, centrifuge at 9000 rpm for 15 minutes to isolate the nanoparticle product.
[0064] 1.3) Ultrasonicating the nanoparticles obtained in step 1.2) for 30 minutes using a mixture of ethanol and acetone (volume ratio of 2:1) as an extractant to remove residual F127 and TMB; repeating this washing process three times, and collecting by centrifugation to obtain mesoporous polydopamine nanoparticles (mPDA NPs);
[0065] 2) Preparation of mPDA@NO nanoparticles by nitrosation
[0066] 2.1) Ultrasonic dispersion of 50 mg of the mPDA nanoparticles obtained in step 1) in an aqueous solution of sodium nitrite (2.4% w / v) to obtain a mixture;
[0067] 2.2) The mixture obtained in step 2.1) was added dropwise to 60 ml of 3 M sulfuric acid in an ice bath, stirred evenly, and then placed in a sealed container to react for 8 hours. After the reaction was complete, the mixture was centrifuged at 11,000 rpm for 30 minutes to isolate the product;
[0068] 2.3) Washing the product obtained in step 2.2) with water and acetone to ensure complete removal of NaNO2 (to test whether NaNO2 is completely removed, the supernatant after centrifugation can be tested using the Griess method; if there is no absorption peak at 540 nm, it indicates complete removal), thereby obtaining modified mesoporous polydopamine nanoparticles with nitric oxide release function, i.e., mPDA@NO nanoparticles.
[0069] 3) Preparation of mPDA@NO-ROX nanoantibacterial agent
[0070] The mPDA@NO nanoparticles obtained in step 2) were dispersed in a ROX solution with a mass concentration of 0.4 mg / mL (the mass ratio of mPDA@NO nanoparticles to ROX was 1:4); after stirring for 24 hours, the mixture was centrifuged to separate the nanoparticle product to obtain the mPDA@NO-ROX nano-antibacterial agent.
[0071] Verification Example 1
[0072] Step 1) is the same as in Example 1;
[0073] Step 2) Preparation of mPDA-ROX nanoparticles
[0074] 2 mg of mPDA nanoparticles were dispersed in 10 mL of ROX solution (multiple samples were prepared using ROX solutions of different concentrations, 0.1, 0.2, 0.4, 0.6, and 0.8 mg / mL). After stirring for 24 h, the mixture was centrifuged to obtain the nanoparticle product, mPDA-ROX nanoparticles.
[0075] In order to verify the performance of the nano antibacterial agent, the present invention also conducted the following tests on the mPDA@NO-ROX nano antibacterial agent prepared in Example 1:
[0076] from Figure 1 It can be seen that in Example 1, the nitric oxide (NO) donor group is modified on the dopamine molecule, and the prepared mPDA@NO-ROX surface releases NO after being irradiated by NIR. At the same time, the ROX molecules are adsorbed in the mesopores of the polydopamine particles through the π-π stacking effect between them.
[0077] from Figure 2 From the scanning electron microscope (SEM) images, it can be seen that the mPDA particles before modification in Example 1 showed a surface morphology with uniformly distributed mesopores. After loading with NO donor and ROX, the particle size of the polydopamine nanoparticles did not change significantly, but its surface morphology changed, and no pore structure similar to that before loading was observed, indicating that the pores of the nanoparticles were filled with NO donor and ROX.
[0078] from Figure 3 The nitrogen adsorption-desorption curve of the mPDA mesoporous material before modification in Example 1 can show a type IV isotherm curve of the mesoporous material, and its specific surface area is 35.2978 m 2 The pore size distribution ranges from 3 to 32 nm, with an average pore size of approximately 30 nm, further confirming that it has large pore channels, which is conducive to efficient drug loading.
[0079] from Figure 4 It can be seen that in Example 1, as the mPDA nanoparticles were surface-modified with NO donors and further subjected to ROX adsorption treatment, the hydrated particle size of the nanoparticles increased significantly, indicating that NO donors and ROX were loaded on the surface and in the mesopores of the mPDA nanoparticles.
[0080] right Figure 5 X-ray photoelectron spectroscopy (XPS) analysis of the mPDA@NO-ROX nanoparticles in Example 1 revealed characteristic peaks for arsenic (As(3d), indicating successful adsorption of ROX into the surface mesopores. Furthermore, a new peak at 406.1 eV emerged in the XPS spectrum of the mPDA@NO nanoparticle surface, originating from N=O, demonstrating successful surface loading of NO donor groups onto the mPDA nanoparticles.
[0081] right Figure 6 Compared with the ultraviolet absorption spectra (UV-vis) of the mPDA@NO-ROX nanoparticles in Example 1, the mPDA@NO-ROX nanoparticles in Example 1 have an obvious ROX characteristic absorption peak at 337 nm compared with the others, indicating that ROX is successfully adsorbed into the pores of the mPDA nanoparticles.
[0082] Depend on Figure 7 As shown in the figure, the absorption amount of ROX in Verification Example 1 increases with the increase of its ratio to mPDA. However, after the ratio reaches 3, the absorption amount does not change much because the adsorption of ROX in the cavities is close to saturation, and the overall loading efficiency also decreases.
[0083] Depend on Figure 8 As shown in the NIR controlled-release test of mPDA-ROX (mPDA:ROX weight ratio of 1:4) in Validation Example 1, the release rate gradually increased over time. Under near-infrared (NIR) irradiation, the drug release rate was significantly increased, indicating that the ROX-loaded mPDA-ROX nanoparticles possess significant photothermal controlled-release properties, allowing them to rapidly release more bactericidal drugs in a short period of time under NIR stimulation.
[0084] Depend on Figure 9 As shown in the figure, in the absence of NIR irradiation, the amount of NO released is almost 0, while in the case of NIR irradiation, the amount of NO released from the donor group gradually increases with the extension of irradiation time, and the increase slows down after 15 minutes; this shows that mPDA@NO nanoparticles have very obvious performance of photothermal conversion to control NO release.
[0085] Depend on Figure 10 As shown, using Triton X-100-treated red blood cell suspension as a control, the experimental results showed that the hemolysis rate of mPDA@NO-ROX nanoparticles reached a maximum of 9.5% when the mass concentration was as high as 4 mg / mL, and was less than 5% when the mass concentration was below 1 mg / mL, indicating that it has good blood compatibility at this concentration.
[0086] Depend on Figure 11 As shown in the data, under normal circumstances, there is little difference in the bactericidal effects. However, under NIR irradiation, differently modified mPDA nanoparticles (all at a concentration of 1 mg / mL) all exhibited better bactericidal effects. At the same time, mPDA@NO-ROX nanoparticles exhibited more significant antibacterial effects than mPDA nanoparticles loaded with NO donors or adsorbed with ROX. This indicates that simultaneous loading of NO donors and ROX can better kill drug-resistant bacteria, and achieves the function of precise and controllable killing of drug-resistant bacteria through synergistic chemo-photothermal therapy.
[0087] It can be seen that the nano antibacterial agent designed by the present invention using the concept of new use of old drugs has potential application prospects in the field of combating drug-resistant bacterial infections.
[0088] The above description is only a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with this technical field can easily think of various equivalent modifications or replacements within the technical scope disclosed in the present invention, and these modifications or replacements should all be included in the scope of protection of the present invention.
Claims
1. A mesoporous polydopamine nano-antibacterial agent loaded with an organic arsenic agent, characterized in that: The nano antibacterial agent has a particle size of 20 to 200 nm and uses mesoporous polydopamine nanoparticles modified with nitric oxide donor groups as a carrier, and an organic arsenic fungicide is adsorbed in the mesopores and on the surface of the carrier; the nitric oxide donor groups are derived from sodium nitrite; and the organic arsenic fungicide is roxarsone. The nitric oxide donor group is loaded on the secondary amine active site of the mesoporous polydopamine nanoparticles through a nitrosation reaction, thereby modifying the mesoporous polydopamine nanoparticles; When the nano antibacterial agent is irradiated with near-infrared light, the mesoporous polydopamine nanoparticles can promote the release of nitric oxide and organic arsenic fungicide while performing photothermal antibacterial treatment.
2. The method for preparing the organic arsenic loaded mesoporous polydopamine nano antibacterial agent according to claim 1, characterized in that: The following steps are involved: 1) Preparation of modified mesoporous polydopamine nanoparticles The modified mesoporous polydopamine nanoparticles with nitric oxide release function, namely mPDA@NO nanoparticles, were obtained by loading nitric oxide donor groups on the secondary amine active sites of mesoporous polydopamine nanoparticles with a particle size of 20-200 nm through a nitrosation reaction. 2) Preparation of nano antibacterial agents The modified mesoporous polydopamine nanoparticles obtained in step 1) adsorb the organic arsenic fungicide in the mesopores and on the surface, thereby obtaining a nano antibacterial agent that can simultaneously release nitric oxide and the organic arsenic fungicide under near-infrared light irradiation.
3. The preparation method according to claim 2, characterized in that: Step 1) is specifically as follows: 1.1) ultrasonically dispersing mesoporous polydopamine nanoparticles having a particle size of 20-200 nm in an aqueous solution of sodium nitrite to obtain a mixture; 1.2) adding the mixture obtained in step 1.1) dropwise to sulfuric acid in an ice bath, stirring evenly, and placing in a sealed container for reaction. After the reaction is complete, centrifugation is performed to obtain the product; 1.3) Washing the product obtained in step 1.2) with water and acetone to ensure that NaNO2 is completely removed, thereby obtaining modified mesoporous polydopamine nanoparticles with nitric oxide release function.
4. The preparation method according to claim 3, characterized in that Step 2) is specifically as follows: The modified mesoporous polydopamine nanoparticles obtained in step 1) are dispersed in an organic arsenic fungicide solution, stirred evenly to allow the organic arsenic fungicide to adsorb on the mesopores and surface of the nanoparticles, and centrifuged to obtain a mesoporous polydopamine nanoantibacterial agent loaded with organic arsenic.
5. The preparation method according to claim 4, characterized in that: In step 1), the preparation method of mesoporous polydopamine nanoparticles with a particle size of 20-200 nm is as follows: S1. The emulsifier triblock copolymer F127 and 1,3,5-trimethylbenzene TMB were dissolved in a mixed solution of water and ethanol, stirred until the emulsifier was uniformly dispersed, and tris(hydroxymethyl)aminomethane TRIS solution was added to adjust the pH of the mixed solution to 7-8; S2 adds dopamine hydrochloride to the mixed solution obtained in S1, stirs and reacts, and after the reaction is complete, centrifuges and collects the nanoparticle product; S3 uses a mixture of ethanol and acetone as an extractant to ultrasonically treat the nanoparticle product obtained in S2 to remove the triblock copolymer F127 and TMB; repeat the washing process multiple times, and collect by centrifugation to obtain mesoporous polydopamine nanoparticles.
6. The preparation method according to claim 5, characterized in that: In S1, the mass ratio of F127 to TMB was 1:1, and the concentration was adjusted to 0.64% (w / v) with water and ethanol, and the volume ratio of water to ethanol was 13:12; the emulsifier was evenly dispersed by stirring for half an hour; In S2, the weight ratio of dopamine hydrochloride to the total weight of F127 and TMB was 1:13.3; the reaction was stirred for 24 hours, and the centrifugation speed was 9000 rpm for 15 minutes; In S3, the volume ratio of ethanol to acetone is 2:1; the washing process is repeated 3 times.
7. The preparation method according to claim 6, characterized in that: In step 1.1), the mass concentration of the aqueous solution of sodium nitrite is 2.4% (w / v); The mass ratio of mesoporous polydopamine nanoparticles to sodium nitrite is 1:5-10; In step 1.2), the volume ratio of sulfuric acid to the mixture in step 1.1) is 6:1 to 5:1, and the molar concentration of sulfuric acid is 3M; The reaction was carried out for 7-10 hours, the centrifugal speed was 11000 rpm, and the centrifugal time was 25-35 minutes.
8. The preparation method according to claim 7, characterized in that: In step 2), the organic arsenic fungicide solution is a roxarsone solution with a mass concentration of 0.1-0.8 mg / mL; The mass ratio of modified mesoporous polydopamine nanoparticles to roxarsone solution is 1:0.5-4; Stir evenly for 22 to 24 hours.
Citation Information
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