Mangiferin / vanadium / PVP (Polyvinyl Pyrrolidone) composite nanoparticle as well as preparation method and application thereof

Abstract

The invention discloses mangiferin / vanadium / PVP (Polyvinyl Pyrrolidone) composite nanoparticles as well as a preparation method and application thereof, and belongs to the field of nano medical materials. The composite nano particle disclosed by the invention is formed by self-assembling mangiferin, vanadium trichloride hexahydrate and polyvinyl pyrrolidone under the coordination action. The preparation method is simple and convenient, conditions are mild, the prepared nanoparticles are uniform in particle size, have good water dispersibility and photothermal conversion performance and have inherent bacteriostatic activity on various bacteria, and the antibacterial effect can be synergistically enhanced under irradiation of near-infrared light. The material has application prospects in the biomedical fields of antibiosis, photo-thermal therapy preparations and the like.

Description

Technical Field

[0001] This invention belongs to the field of nanomedicine materials, specifically relating to a mangiferin / vanadium / PVP composite nanoparticle, its preparation method, and its application. Background Technology

[0002] Mangiferin is a natural flavonoid compound with various bioactivities, including antibacterial, anti-inflammatory, and antioxidant properties. However, its poor water solubility and low bioavailability limit its application in the pharmaceutical field. In recent years, the direct self-assembly of functional nanomaterials using the coordination of polyphenolic compounds with metal ions has emerged as a new research direction. This approach promises to improve solubility while also endowing materials with better stability and controllability. However, existing research largely focuses on a few metal systems such as iron and copper, and the functions of the developed materials are often limited to single-function chemotherapeutic treatments or deliveries, proving insufficient for addressing complex biomedical needs.

[0003] Photothermal therapy, as a non-invasive treatment method, has received widespread attention in the fields of antibacterial and antitumor applications. Its principle is to utilize photothermal materials to convert light energy into heat energy, achieving precise physical therapy on the lesion site. Although mangiferin possesses inherent bactericidal capabilities, it lacks efficient photothermal conversion performance and therefore cannot be directly applied to the field of photothermal therapy.

[0004] Currently, no mangiferin-based nanomaterials with good biocompatibility, stability, and photothermal properties have been reported. Summary of the Invention

[0005] The technical problem to be solved by the present invention is that existing mangiferin-based antibacterial materials have limited functions and are difficult to achieve synergistic physical therapy.

[0006] To achieve the above-mentioned objectives, the technical solution adopted in this application is as follows.

[0007] In a first aspect, the present invention provides a mangiferin / vanadium / PVP composite nanoparticle, wherein the composite nanoparticle is composed of mangiferin, vanadium, and PVP. 3+ MGF-V formed through coordination with polyvinylpyrrolidone 3+ -PVP complex.

[0008] Furthermore, the particle size of the aforementioned mangiferin / vanadium / PVP composite nanoparticles is 20~65nm.

[0009] Secondly, the present invention provides a method for preparing the above-mentioned mangiferin / vanadium / PVP composite nanoparticles, comprising the following steps: S1. Dissolve VCl3·6H2O and polyvinylpyrrolidone in an appropriate amount of deionized water, stir and mix to obtain a mixture; S2. Dissolve mangiferin in an appropriate amount of ethanol, stir and mix well to obtain a mangiferin ethanol solution; S3. Add the mangiferin ethanol solution dropwise to the mixture and stir the reaction thoroughly to obtain a mangiferin / vanadium / PVP composite nanoparticle dispersion. After dialysis purification and freeze-drying, solid mangiferin / vanadium / PVP composite nanoparticles are obtained.

[0010] In step S1 above, the mass ratio of VCl3·6H2O to polyvinylpyrrolidone is 1:3 to 1:4.

[0011] In step S2 above, the mass ratio of VCl3·6H2O to mangiferin is 1:0.35~1:0.55.

[0012] In step S2 above, the concentration of the mangiferin ethanol solution is 8~12 mg / mL.

[0013] In step S2 above, the stirring reaction time is 2 to 4 hours.

[0014] Thirdly, the present invention provides the application of the above-mentioned mangiferin / vanadium / PVP composite nanoparticles in the preparation of antibacterial and / or photothermal therapy products.

[0015] Furthermore, the antibacterial properties include the ability to inhibit or kill at least one of the following microorganisms: Staphylococcus aureus, epidermal bacteria, Streptococcus sanguinis, Escherichia coli, and Amoeba.

[0016] Furthermore, the photothermal therapy includes the use of the photothermal effect generated by mangiferin / vanadium / PVP composite nanoparticles under near-infrared light irradiation at a wavelength of 808 nm to inhibit or kill at least one of the following microorganisms: Staphylococcus aureus, epidermal bacteria, Streptococcus sanguinis, Escherichia coli, and Amoeba.

[0017] The beneficial effects of this invention: This invention provides a mangiferin / vanadium / PVP composite nanoparticle and its preparation method. Stable MGF-V nanoparticles are obtained by coordinating VCl3·6H2O, mangiferin, and polyvinylpyrrolidone in a specific ratio. 3+ -PVP complex. This composite nanoparticle exhibits excellent water dispersibility and photothermal conversion properties, demonstrating significant inherent antibacterial activity against various common pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. Furthermore, under 808nm near-infrared light irradiation, its antibacterial performance is further enhanced through a synergistic effect between the photothermal effect and its inherent antibacterial activity. Attached Figure Description

[0018] Figure 1 MGF-V 3+ Characterization results of PVP composite nanoparticles; Figure A shows MGF-V. 3+ - Particle size distribution of PVP composite nanoparticles, Figure B shows the particle size distribution of MGF-V 3+ -UV-Vis absorption spectrum of PVP composite nanoparticles; Figure 2 MGF-V 3+ - SEM image of PVP composite nanoparticles; Figure 3 MGF-V 3+ - The antibacterial effect of PVP composite nanoparticles on five tested bacterial strains. Figure 4 MGF-V 3+ - The antibacterial effect of PVP composite nanoparticles on two tested bacterial strains. Figure A shows the antibacterial effect of Escherichia coli, and Figure B shows the antibacterial effect of Staphylococcus aureus. Figure 5 For different concentrations of MGF-V 3+ - Temperature change curve of PVP nanoparticle solution under 808nm laser irradiation; Figure A shows MGF-V at a concentration of 7.5 mg / mL. 3+ -PVP composite nanoparticle solution, Figure B shows 1.75 mg / mL MGF-V 3 + -PVP composite nanoparticle solution, Figure C is deionized water; Figure 6 The curves show the changes in bacterial survival rate over time under different conditions. Detailed Implementation

[0019] To make the technical problems, solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with the embodiments. Unless otherwise defined, all technical terms used herein have the same meaning as understood by one of ordinary skill in the art.

[0020] This invention discloses a mangiferin / vanadium / PVP composite nanoparticle, wherein the composite nanoparticle is composed of mangiferin (MGF) and trivalent vanadium ions (PVP). 3+ It is prepared from MGF and polyvinylpyrrolidone (PVP), wherein the catechol group in the MGF molecule and the carbonyl group on the PVP molecule chain are respectively related to V 3+ Coordination, forming MGF-V 3+ -PVP nanostructure. The MGF-V 3+ -PVP composite nanoparticles have good water dispersibility, with a particle size distribution range of 20 to 65 nanometers and an average particle size of about 40 nanometers.

[0021] The MGF-V3+ - In PVP composite nanoparticles, MGF and V 3+ Together they provide biological activity, and V 3+ The introduction of this technology simultaneously endows the material with photothermal conversion capabilities. Experiments show that the MGF-V... 3+ - The PVP complex has significant inhibitory and bactericidal effects on common pathogenic microorganisms such as Escherichia coli and Staphylococcus aureus. Furthermore, its antibacterial activity can be synergistically enhanced under near-infrared light irradiation due to the photothermal effect.

[0022] This invention also discloses a method for preparing mangiferin / vanadium / PVP composite nanoparticles. The specific steps are as follows: dissolving VCl3·6H2O and polyvinylpyrrolidone in an appropriate amount of deionized water and stirring to obtain a mixed solution; dissolving mangiferin in an appropriate amount of ethanol and stirring to obtain a mangiferin ethanol solution; adding the mangiferin ethanol solution dropwise to the mixed solution and stirring thoroughly to obtain MGF-V 3+ The PVP composite nanoparticle dispersion was purified by dialysis and freeze-dried to obtain solid MGF-V. 3+ -PVP composite nanoparticles.

[0023] The core of the preparation method described in this invention lies in stepwise mixing. The ethanol solution of mangiferin is added dropwise to an aqueous phase containing vanadium and PVP, which facilitates controlled coordination and assembly at the interface, avoiding the formation of irregular large particles due to rapid precipitation. Prolonged gentle stirring at room temperature provides conditions for sufficient intermolecular coordination and uniform growth of nanoparticles. The preparation method of this invention does not require harsh reaction conditions (such as high temperature, high pressure, or inert atmosphere) or complex post-treatment purification steps, exhibiting good process operability and suitability for industrial production.

[0024] The following specific embodiments will be provided to explain the solution of the present invention. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0025] Example 1: Preparation of mangiferin / vanadium / PVP composite nanoparticles.

[0026] (1) This embodiment sets up three groups of experiments, and the raw material ratios are as follows: Experiment 1-1: Take 0.4026g VCl3·6H2O, 0.216g MGF, 1.2078g PVP and an appropriate amount of deionized water; Experiment 1-2: Take 0.4026g VCl3·6H2O, 0.144g MGF, 1.6104g PVP and an appropriate amount of deionized water; Experiments 1-3: Take 0.4026g VCl3·6H2O, 0.1816g MGF, 1.3221g PVP and an appropriate amount of deionized water.

[0027] (2) Preparation process: Add 4 mL of deionized water to VCl3·6H2O and stir until fully dissolved to obtain an aqueous solution of VCl3. Add 176 mL of deionized water to PVP and stir until fully dissolved to obtain an aqueous solution of PVP. Mix the VCl3 aqueous solution and the PVP aqueous solution and stir at room temperature for 0.5 h until homogeneous to obtain a VCl3 / PVP mixture.

[0028] MGF was added to 18 mL of anhydrous ethanol and stirred until fully dissolved to obtain an MGF ethanol solution. The MGF ethanol solution was then added dropwise to a VCl3 / PVP mixture. After the addition was complete, the mixture was stirred at room temperature for 3 hours. The system gradually darkened in color, indicating that MGF-V... 3+ -PVP composite nanoparticles are formed to obtain a coarse dispersion.

[0029] The obtained crude dispersion was transferred to a dialysis bag and purified by dialysis using a large amount of deionized water as the dialysis fluid to remove unreacted ions and small molecule impurities. Dialysis was performed in 2 L of deionized water for 24 hours, with the dialysis fluid changed every 4 hours. The dialysis solution was then freeze-dried to obtain solid MGF-V. 3+ -PVP composite nanoparticles.

[0030] Example 2: Detection of mangiferin / vanadium / PVP composite nanoparticles.

[0031] (1) MGF-V was prepared in the example 3+ The characterization results of the PVP composite nanoparticles are as follows: Figure 1 As shown; where Figure A is MGF-V 3+ - Particle size distribution of PVP composite nanoparticles, Figure B shows the particle size distribution of MGF-V 3+ -UV-Vis absorption spectrum of PVP composite nanoparticles. As shown in Figure A, the MGF-V prepared in this invention... 3+ The particle size of the PVP composite nanoparticles is mainly concentrated in the range of 20-50 nm, with a relatively high proportion of particles around 40 nm. The overall distribution is relatively concentrated (no extreme dispersion was observed), indicating that the composite nanoparticles prepared by this invention have good particle size uniformity. As shown in Figure B, the MGF-V... 3+- PVP composite nanoparticles have obvious absorption peaks in the range of 300nm to 850nm, and strong absorption below 500nm.

[0032] (2) MGF-V was prepared in the example 3+ -SEM images of PVP composite nanoparticles as shown Figure 2 As shown in the figure. It can be seen from the figure that the MGF-V 3+ - PVP composite nanoparticles are irregularly shaped particles with an overall size in the nanometer range.

[0033] (3) Solid culture medium test: The MGF-V prepared in Example 1 was used to test the solid culture medium. 3+ - PVP composite nanoparticles were added to deionized water to prepare MGF-V at a concentration of 4 mg / mL. 3+ - PVP composite nanoparticle solution, ready for use. After sterilizing the agar plate, allow the surface moisture to evaporate. Using a quantitative pipette, pipette 30 μL each of *Escherichia coli*, *Staphylococcus aureus*, *Amoeba histolytica*, *Streptococcus sanguinis*, and epidermal bacteria, and add them separately to the surface of the agar plate to form uniform bacterial patches with a diameter of 5–8 mm. After the bacterial solutions are completely absorbed by the agar, take 50 μL of PVP composite nanoparticle solution... 3+ - PVP composite nanoparticle solution was dropped onto a 10 mm diameter sterile filter paper plate laid flat on the bacterial plaque. Then the agar plate was inverted and incubated in a constant temperature incubator at 35±2℃ for 16~20 h.

[0034] MGF-V 3+ - The antibacterial effect of PVP composite nanoparticles on five tested bacterial strains is as follows: Figure 3 As shown in the figure, on the culture dishes corresponding to the 5 strains, 3 contained MGF-V. 3+ The presence of clear and transparent antibacterial zones around the filter paper containing the PVP composite nanoparticles indicates that mangiferin carbon dots have significant antibacterial activity against Escherichia coli, Staphylococcus aureus, Amoeba, Streptococcus sanguinis, and epidermal bacteria.

[0035] (4) Liquid culture medium test: The MGF-V prepared in Example 1 was used to test the liquid culture medium. 3+ PVP composite nanoparticles were precisely weighed according to different masses and added to equal volumes of *E. coli* and *Staphylococcus aureus* bacterial suspensions, respectively. The mixtures were then agitated to disperse the nanoparticles and ensure uniform suspension. The final concentrations of the composite nanoparticles in the systems were 0, 400, 600, 800, 1000, and 1200 μg / mL, respectively. The bacterial suspensions containing different masses of composite nanoparticles were then dynamically cultured (37℃), with samples taken at time intervals of 0–18 h. Oddi concentrations were then analyzed using OD0.05... 600 The bacterial concentration at each time point was determined by the method.

[0036] MGF-V 3+-The antibacterial effect of PVP composite nanoparticles on the two tested strains is as follows: Figure 4 As shown in the figures; Figure A shows the antibacterial effect against Escherichia coli, and Figure B shows the antibacterial effect against Staphylococcus aureus. As can be seen from the figures, MGF-V... 3+ - The higher the PVP concentration, the flatter the corresponding OD curve rises, indicating a stronger antibacterial effect.

[0037] (5) Photothermal conversion test: The MGF-V prepared in Example 1 was tested. 3+ - PVP composite nanoparticles were added to deionized water to prepare MGF-V at concentrations of 1.75 mg / mL and 7.5 mg / mL. 3+ - PVP composite nanoparticle solution, for later use. A deionized water blank group was also prepared. Solutions of various concentrations were placed in the same container as the blank group solution, and irradiated with an 808nm near-infrared laser under controlled conditions. Temperature changes in each system were monitored and recorded in real time at different time points during the process.

[0038] Different concentrations of MGF-V 3+ The temperature-time curve of the PVP nanoparticle solution under 808nm laser irradiation is shown below. Figure 5 As shown; where Figure A shows 7.5 mg / mL MGF-V 3+ -PVP composite nanoparticle solution, Figure B shows 1.75 mg / mL MGF-V 3 + - PVP composite nanoparticle solution, Figure C shows deionized water. As can be seen from the figure, at the same nanoparticle concentration, the higher the laser power, the faster the solution heats up and the higher the final temperature; at the same power, the higher the nanoparticle concentration, the stronger the heating effect. The temperature rise of deionized water is much lower than that of the nanoparticle solution, indicating that the temperature rise is mainly due to MGF-V... 3+ - The photothermal effect of PVP composite nanoparticles contributes to its ability to convert light energy into heat energy under 808nm laser irradiation.

[0039] (6) Synergistic antibacterial ability test: The MGF-V prepared in Example 1 was used to test the synergistic antibacterial ability. 3+ PVP composite nanoparticles were added to equal volumes of E. coli bacterial culture, and dispersed by shaking to ensure uniform suspension of the nanoparticles. The final concentration of the composite nanoparticles in the system was 2 mg / mL. Three parallel experiments were set up: ① Illuminated group: the mixture was irradiated under an 808 nm near-infrared laser; ② Unilluminated group: all conditions were identical to ① except for the absence of illumination; ③ Unilluminated control group: an equal volume of deionized water was used instead of the nanoparticle stock solution, mixed with the bacterial culture, and irradiated with an 808 nm laser under the same conditions. All groups were continuously cultured at 37℃ with shaking, and samples were taken at time intervals from 0 to 8 hours to test the bacterial survival rate at each time point.

[0040] The curves showing the change in bacterial survival rate over time under different conditions are as follows: Figure 6 As shown in the figure, the bacterial survival rate in the group without material illumination remained at around 0.9, indicating that light alone had almost no killing effect on bacteria; the bacterial survival rate in the group without material illumination decreased over time (to about 0.2 after 8 hours), indicating that MGF-V... 3+ - PVP composite nanoparticles themselves possess antibacterial activity; the bacterial survival rate decreased the fastest in the material irradiation group (approximately 0.1% after 8 hours), indicating that under 808nm near-infrared light irradiation, MGF-V... 3+ The antibacterial properties of PVP composite nanoparticles are synergistically enhanced due to their photothermal effect.

Claims

1. A mangiferin / vanadium / PVP complex nanoparticle characterized in that: The complex nanoparticles are MGF-V-PVP complex formed by coordination of mangiferin, V 3+ and polyvinylpyrrolidone. 3+ -PVP complex.

2. The complex nanoparticles of mangiferin / vanadium / PVP according to claim 1, characterized in that: The composite nanoparticles have a particle size of 20-65 nm.

3. A method for preparing mangiferin / vanadium / PVP composite nanoparticles, characterized in that, The method comprises the following steps: S1. Dissolving VCl3·6H2O and polyvinylpyrrolidone in a proper amount of deionized water, mixing and stirring to obtain a mixed solution; S2. Dissolving mangiferin in a proper amount of ethanol, mixing and stirring to obtain a mangiferin ethanol solution; S3. Adding the mangiferin ethanol solution dropwise into the mixed solution, fully stirring and reacting to obtain a mangiferin / vanadium / PVP composite nanoparticle dispersion, which is purified by dialysis and freeze-dried to obtain solid mangiferin / vanadium / PVP composite nanoparticles.

4. The method of claim 3, wherein the preparation of the complex nanoparticles of mangiferin / vanadium / PVP is characterized by: In step S1, the mass ratio of VCl3·6H2O to polyvinylpyrrolidone is 1:3-1:

4.

5. The method of claim 3, wherein the preparation of the complex nanoparticles of mangiferin / vanadium / PVP is characterized by: In step S2, the mass ratio of VCl3·6H2O to mangiferin is 1:0.35-1:0.

55.

6. The method of claim 3, wherein the preparation of the complex nanoparticles of mangiferin / vanadium / PVP is characterized by: In step S2, the concentration of the mangiferin ethanol solution is 8-12 mg / mL.

7. The method of claim 3, wherein the preparation of the complex nanoparticles of mangiferin / vanadium / PVP is characterized by: In step S2, the stirring and reaction time is 2-4 hours.

8. The mangiferin / vanadium / PVP composite nanoparticles of claim 1 or 2, or the mangiferin / vanadium / PVP composite nanoparticles prepared by the method of any one of claims 3-7, for use in the preparation of an antibacterial and / or photothermal therapy product.

9. Use according to claim 8, characterized in that: The antibacterial effect includes inhibiting or killing at least one of Staphylococcus aureus, epidermis bacteria, Streptococcus sanguis, Escherichia coli and amoeba.

10. Use according to claim 8, characterized in that: The photothermal therapy includes using the photothermal effect of the mangiferin / vanadium / PVP composite nanoparticles to inhibit or kill at least one of Staphylococcus aureus, epidermis bacteria, Streptococcus sanguis, Escherichia coli and amoeba under the irradiation of near-infrared light with a wavelength of 808 nm.

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