A cof hydrogel material, a preparation method and application in a photothermal sterilization material

Abstract

The application discloses a COF hydrogel material, a preparation method thereof and application of the COF hydrogel material in a photothermal sterilization material. The preparation method of the COF hydrogel material comprises the following steps: reacting aldehyde group monomers including monoaldehyde and dialdehyde and amino monomers through a solvothermal method to obtain a covalent organic framework (COF); and reacting the COF and hyaluronic acid through an amide condensation reaction to obtain the COF hydrogel material. The COF hydrogel material has good photothermal conversion performance under 808 nm infrared light irradiation, thus having excellent photothermal sterilization performance and good water dispersibility.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and particularly relates to a COF hydrogel material, its preparation method, and its application in photothermal sterilization materials. Background Technology

[0002] Covalent organic frameworks (COFs) are crystalline materials with periodic porous structures formed by small organic molecules linked by covalent bonds. Due to their high specific surface area, tunable pore size, structural diversity, and good chemical stability, they have been widely studied in gas adsorption, catalysis, sensing, and optoelectronics. In recent years, their application potential in photothermal conversion has also gradually emerged. By controlling the conjugated framework structure of COFs, such as by introducing large π-conjugated units like porphyrins, broad-spectrum absorption in the visible to infrared light region can be achieved, laying the foundation for efficient photothermal conversion. Currently, some COFs have been proven to generate heat under infrared light irradiation, showing potential for application in photothermal therapy. However, COFs prepared by traditional solvothermal methods are basically in powder form with poor water dispersibility, which limits their application in the biomedical field. Therefore, it is necessary to design a COF with good water dispersibility for photothermal therapy in biological systems. Summary of the Invention

[0003] Based on the above-mentioned technical problems, the present invention provides a COF hydrogel material, a preparation method thereof, and its application in photothermal sterilization materials. The COF hydrogel material has good photothermal conversion performance under 808 nm infrared light irradiation, thereby exhibiting excellent photothermal sterilization performance and good water dispersibility.

[0004] The present invention proposes a method for preparing COF hydrogel material, comprising the following steps:

[0005] S1. After reacting aldehyde monomers, including monoaldehydes and dialdehydes, and amino monomers via a solvothermal method, a covalent organic framework (COF) is obtained.

[0006] S2. The covalent organic framework (COF) and hyaluronic acid are subjected to an amide condensation reaction to obtain the COF hydrogel material.

[0007] Preferably, the monoaldehyde is at least one of 4-methoxybenzaldehyde, p-hydroxybenzaldehyde, or 2,5-dihydroxybenzaldehyde, and more preferably 2,5-dihydroxybenzaldehyde; the dialdehyde is at least one of terephthalaldehyde, 2,5-dimethoxyterephthalaldehyde, 2,2'-bipyridine-5,5'-dicarboxaldehyde, or 2,5-dihydroxyterephthalaldehyde, and more preferably 2,5-dihydroxyterephthalaldehyde.

[0008] Preferably, the molar ratio of the monoaldehyde and dialdehyde is 1:2-4.

[0009] Preferably, the amino monomer is at least one of 1,3,5-tris(4-aminophenyl)benzene, 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, or 5,10,15,20-tetra(4-aminophenyl)-21H,23H porphyrin, preferably 5,10,15,20-tetra(4-aminophenyl)-21H,23H porphyrin.

[0010] Preferably, the molar ratio of the aldehyde monomer to the amino monomer is 1-3:1.

[0011] Preferably, in step S1, the temperature of the solvothermal reaction is 100-150 °C and the time is 60-84 h;

[0012] Preferably, the solvothermal reaction is carried out under acidic conditions, and the reaction solvent is o-dichlorobenzene and n-butanol in a volume ratio of 1:1.

[0013] Preferably, the mass ratio of the covalent organic framework (COF) to hyaluronic acid is 1:4-6.

[0014] Preferably, in step S2, the amide condensation reaction is carried out under a condensation reagent, which is at least one of 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, or N-hydroxysuccinimide, preferably 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide;

[0015] Preferably, the mass ratio of hyaluronic acid to 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is 1:5-15, and the mass ratio of hyaluronic acid to N-hydroxysuccinimide is 1:4-8.

[0016] This invention also proposes a COF hydrogel composite material prepared by the above preparation method.

[0017] The present invention also proposes an application of the above-mentioned COF hydrogel composite material in photothermal bactericidal materials.

[0018] This invention provides a covalent organic framework material with a gel morphology that can generate heat upon light irradiation. A COF containing numerous amino defects is prepared by reacting a mixed aldehyde monomer (monoaldehyde and dialdehyde) with an amino monomer under solvothermal conditions. Then, the exposed amino groups in the COF structure undergo an amide condensation reaction with the abundant carboxyl groups in hyaluronic acid, covalently linking the COF to hyaluronic acid to obtain a COF hydrogel material. This material retains the conjugated extended structure and porphyrin structure of the COF, thus exhibiting excellent photothermal conversion performance. Simultaneously, the hydrogel morphology improves the biocompatibility and water dispersibility of the COF, making it more suitable for applications in the biomedical field, such as photothermal sterilization. Attached Figure Description

[0019] Figure 1 The X-ray powder diffraction pattern of COF-366-NH2 described in Example 1 of this invention;

[0020] Figure 2 These are visual morphological images of COF-366-HA before (left) and after (right) freeze-drying as described in Embodiment 1 of the present invention;

[0021] Figure 3 The X-ray powder diffraction pattern of COF-366-HA described in Example 1 of this invention;

[0022] Figure 4 This is a transmission electron microscope image of COF-366-HA as described in Example 1 of the present invention;

[0023] Figure 5 This is a scanning electron microscope image of COF-366-HA as described in Embodiment 1 of the present invention;

[0024] Figure 6 The UV-Vis spectrum of COF-366-HA described in Example 1 of this invention;

[0025] Figure 7 The performance diagram of COF-366-NH2 and COF-366-HA for photothermal conversion described in Embodiment 1 of the present invention is shown.

[0026] Figure 8 This is a real-time image of the COF-366-HA water system described in Embodiment 1 of the present invention heating up under 808 nm light irradiation;

[0027] Figure 9 This is a diagram illustrating the effect of COF-366-HA in photothermal sterilization as described in Embodiment 1 of the present invention. Detailed Implementation

[0028] The present invention will now be described in detail through specific embodiments. However, these examples are clearly provided for illustrative purposes and are not intended to limit the scope of the invention.

[0029] Example 1

[0030] This embodiment proposes a method for preparing COF hydrogel materials, which are prepared by the following method:

[0031] (1) 5,10,15,20-tetra(4-aminophenyl)-21H,23H porphyrin (0.03 mmol) was used as an amino monomer, 2,5-dihydroxyterephthalaldehyde (0.045 mmol) and 2,5-dihydroxybenzaldehyde (0.015 mmol) in a molar ratio of 3:1 were used as aldehyde monomers, 6 M HOAc (0.3 mL) was used as a catalyst, and o-dichlorobenzene and n-butanol (3 mL) in a volume ratio of 1:1 were used as solvents. The mixture was placed in an oven at 120 °C and reacted for 72 h to obtain a solid mixture. After cooling to room temperature, the solid mixture was taken out, washed several times with tetrahydrofuran and ethanol, and dried under vacuum at 60 °C to obtain a covalent organic framework (COF), named COF-366-NH2.

[0032] (2) Dissolve hyaluronic acid (40 mg) in water (2 mL), stir vigorously to make it transparent, add COF-366-NH2 (8 mg), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 416 mg) and N-hydroxysuccinimide (NHS, 232 mg), continue stirring for 10 min, and then place at room temperature for 12 h to obtain a black hydrogel material. Wash with water three times, freeze dry to obtain the COF hydrogel material, named COF-366-HA.

[0033] Figure 1 The X-ray powder diffraction pattern of COF-366-NH2 described in Example 1 of this invention is shown below. Figure 1 It can be seen that the main diffraction peak of COF-366-NH2 is at 2θ = 3.52. o 7.04 o .

[0034] Figure 2 These are intuitive morphological images of COF-366-HA before (left) and after (right) freeze-drying according to Embodiment 1 of the present invention, with reference to... Figure 2 It can be seen that COF-366-HA is a black, non-flowing gel, and the freeze-dried COF-366-HA is light and fluffy.

[0035] Figure 3The X-ray powder diffraction pattern of COF-366-HA described in Example 1 of this invention is shown below. Figure 3 It can be seen that the original COF characteristic diffraction peaks disappeared, while at 22.5... o A broad peak nearby indicates that COF is covalently linked to hyaluronic acid and has a good complexation.

[0036] Figure 4 The image shown is a transmission electron microscope (TEM) image of COF-366-HA as described in Embodiment 1 of this invention, with reference to... Figure 4 It can be seen that COF-366-HA does not have obviously dispersed particles and exhibits a relatively uniform fusion state, indicating that COF and hyaluronic acid are well combined.

[0037] Figure 5 The image shown is a scanning electron microscope (SEM) image of COF-366-HA as described in Embodiment 1 of the present invention, with reference to... Figure 5 It can be seen that the composite hydrogel has a porous structure, an uneven surface, and a loose overall texture with no obvious regular shape.

[0038] Figure 6 The UV-Vis spectrum of COF-366-HA described in Example 1 of this invention is shown below. Figure 6 It can be seen that COF-366-HA has strong absorption in the ultraviolet-visible-near-infrared light regions.

[0039] In this invention, to reveal the photothermal conversion effect of COF-366-HA, COF-366-NH2 and COF-366-HA were used as photothermal materials, and light irradiation experiments were conducted in water and at a wavelength of 808 nm: 5 mg of COF-366-NH2 powder or dried COF-366-HA gel material was weighed and added to 200 μL of deionized water. An 808 nm wavelength laser was used as the light source, and the light intensity was set to 2 W / cm². 2 Light was applied separately, and a thermal imager was used to record the temperature in real time. The results are as follows: Figure 7 and Figure 8 As shown.

[0040] Figure 7 The performance diagram of COF-366-NH2 and COF-366-HA for photothermal conversion described in Embodiment 1 of the present invention is shown below. Figure 7 It can be seen that as the illumination time increases, the water dispersion systems of COF-366-NH2 and COF-366-HA gradually increase in temperature, from about 20 ℃ to about 50 ℃. Moreover, at the same time, the temperature of the COF-366-HA gel material system is always higher than that of the COF-366-NH2 powder system, indicating that after COF reacts with hyaluronic acid, its photothermal conversion performance is retained and improved.

[0041] Figure 8 This is a real-time image of the COF-366-HA water system described in Example 1 heating up under 808 nm light illumination, as shown in the image. Figure 8 It can be seen that the initial temperature was 21.8 ℃, and it rose to 54.2 ℃ after 5 minutes of illumination. The temperature difference before and after 5 minutes of illumination can reach 32.4 ℃, indicating that the COF-366-HA material heats up very quickly.

[0042] Figure 9 The image shown is an illustration of the effect of COF-366-HA in photothermal sterilization as described in Embodiment 1 of the present invention. Figure 9 It can be seen that, compared with the control group, the number of bacterial colonies in the 808 nm light irradiation group and the COF-366-HA treatment group did not change significantly, indicating that simple NIR light irradiation or contact with COF-366-HA cannot produce a significant killing effect on bacteria. In contrast, no bacterial colony formation was observed in the COF-366-HA + light irradiation group, indicating that the high heat generated by COF-366-HA under light irradiation killed almost all bacteria.

[0043] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a COF hydrogel material, characterized in that, Includes the following steps: S1. After reacting aldehyde monomers, including monoaldehydes and dialdehydes, and amino monomers via a solvothermal method, a covalent organic framework (COF) is obtained. S2. The covalent organic framework (COF) and hyaluronic acid are subjected to an amide condensation reaction to obtain the COF hydrogel material.

2. The method for preparing the COF hydrogel material according to claim 1, characterized in that, The monoaldehyde is at least one of 4-methoxybenzaldehyde, p-hydroxybenzaldehyde, or 2,5-dihydroxybenzaldehyde, preferably 2,5-dihydroxybenzaldehyde; the dialdehyde is at least one of terephthalaldehyde, 2,5-dimethoxyterephthalaldehyde, 2,2'-bipyridine-5,5'-dicarboxaldehyde, or 2,5-dihydroxyterephthalaldehyde, preferably 2,5-dihydroxyterephthalaldehyde; Preferably, the molar ratio of the monoaldehyde and dialdehyde is 1:2-4.

3. The method for preparing the COF hydrogel material according to claim 1 or 2, characterized in that, The amino monomer is at least one of 1,3,5-tris(4-aminophenyl)benzene, 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, 2,4,6-tris(4-aminophenyl)-1,3,5-triazine, or 5,10,15,20-tetra(4-aminophenyl)-21H,23H porphyrin, preferably 5,10,15,20-tetra(4-aminophenyl)-21H,23H porphyrin.

4. The method for preparing the COF hydrogel material according to any one of claims 1-3, characterized in that, The molar ratio of the aldehyde monomer to the amino monomer is 1-3:

1.

5. The method for preparing the COF hydrogel material according to any one of claims 1-4, characterized in that, In step S1, the temperature of the solvothermal reaction is 100-150 °C and the time is 60-84 h; Preferably, the solvothermal reaction is carried out under acidic conditions, and the reaction solvent is o-dichlorobenzene and n-butanol in a volume ratio of 1:

1.

6. The method for preparing the COF hydrogel material according to any one of claims 1-5, characterized in that, The mass ratio of the covalent organic framework (COF) to hyaluronic acid is 1:4-6.

7. The method for preparing the COF hydrogel material according to any one of claims 1-6, characterized in that, In step S2, the amide condensation reaction is carried out under a condensation reagent, which is at least one of 4-(4,6-dimethoxytriazine-2-yl)-4-methylmorpholine hydrochloride, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, or N-hydroxysuccinimide, preferably 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide; Preferably, the mass ratio of hyaluronic acid to 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride is 1:5-15, and the mass ratio of hyaluronic acid to N-hydroxysuccinimide is 1:4-8.

8. A COF hydrogel material prepared by the preparation method according to any one of claims 1-7.

9. The application of the COF hydrogel material according to claim 8 in photothermal bactericidal materials.

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