Polyphenol substance surface modified mesoporous nano porous microsphere material as well as preparation method and application thereof
The mesoporous nanoporous microsphere materials with surface modification of polyphenol substances were prepared by cocondensation polymerization, which solved the problem of drug load loss in drug carrier applications, achieved high drug loading rate and good biocompatibility, and was suitable for the preparation of anti-tumor drugs.
Patent Information
- Application Number
- CN202510058231.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-14
- Publication Date
- 2025-06-06
AI Technical Summary
The existing mesoporous microsphere materials have problems with drug load loss in drug carrier applications, resulting in cumbersome operation steps.
By cocondensation polymerization, polyphenol substances such as tanninic acid and dopamine are copolymerized with silicon to prepare mesoporous nanoporous microsphere materials with surface modification of polyphenol substances, and further modified through electrostatic interactions to improve biocompatibility and drug loading capacity.
The high drug loading rate, good dispersion and biocompatibility of mesoporous microsphere materials are achieved, the preparation process is simplified, and the multifunctional properties of the material are enhanced, which is suitable for the preparation of anti-tumor drugs.
Smart Images
Figure CN120093944A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the technical field of ordered mesoporous materials, and in particular to a polyphenol surface-modified mesoporous nanoporous microsphere material and a preparation method and application thereof. Background Art
[0002] Mesoporous materials have gradually become a research hotspot in the field of materials science due to their excellent specific surface area and adjustable microsphere surface pore size, especially in the carriers of active drugs in vivo. The surface of general ordered mesoporous microspheres needs to have small molecules that are easy to modify and degrade as "gatekeepers". However, in the actual drug preparation process, cumbersome operating steps often lead to the loss of drug loading. Therefore, directly combining polyphenol small molecules with "gatekeeper" functions on the surface of mesoporous microspheres can reduce related operations. The present invention selects tannic acid and dopamine as the modifying substances of mesoporous microspheres, which greatly increases the biocompatibility of mesoporous microspheres on the one hand, and can increase the drug load on the other hand.
[0003] To this end, the present invention provides a polyphenol surface modified mesoporous nanoporous microsphere material and a preparation method and application thereof. Summary of the invention
[0004] Based on this, the purpose of the present invention is to provide a polyphenol surface modified mesoporous nanoporous microsphere material and its preparation method and application. The preparation method is simple, the raw materials are low in cost and easy to obtain, and the obtained polyphenol surface modified mesoporous nanoporous microsphere material has good dispersibility, large specific surface area, high drug loading rate, and is green and environmentally friendly.
[0005] In order to achieve the above object, the technical solution of the present invention is as follows:
[0006] According to a first aspect of the present invention, there is provided a method for preparing a polyphenol surface-modified mesoporous nanoporous microsphere material, comprising:
[0007] (1) Using the co-condensation synthesis method, 0.45 g CTAB, 35 mL anhydrous ethanol and 150 mL deionized water were added to a flask and stirred for 30 min at 70 ° C to completely dissolve them; then 12 mL of ammonia water was added to the flask, and the mass fraction of ammonia water was 25%. Then 3.42 g of tetraethyl orthosilicate was added dropwise to the mixed solution. After 5 minutes, 100 mg of polyphenols were added and the reaction was continued by stirring for 24 hours;
[0008] (2) Then centrifuge at 3000 rpm for 5 min, filter, wash with ethanol, and dry at 60 °C. Finally, extract with 200 mL of 10 mg / mL ammonium nitrate ethanol solution at 80 °C for 24 h. Repeat the extraction three times to obtain MSN-PDA.
[0009] (3) Add 20 mL of manganese solution, zinc solution or ferric nitrate solution to 500 mg of MSN-PDA, stir at 30 °C for 24 h, filter, wash and dry to obtain MSN-PDA-Mn, MSN-PDA-Zn and MSN-PDA-Fe.
[0010] In some optional implementations of some embodiments, in step (1), the usage ratio of CTAB, anhydrous ethanol, tetraethyl orthosilicate and polyphenol is 300-450 mg: 35 mL: 12 mL: 3420 mg: 100 mg.
[0011] In some optional implementations of some embodiments, in step (1), the polyphenolic substance is tannic acid and dopamine, and preferably, the polyphenolic substance is dopamine.
[0012] In some optional implementations of some embodiments, in step (3), the concentration of the copper solution or zinc solution or ferric nitrate solution is 0.1 mol / L, and the pH value is 6.0-8.0.
[0013] According to a second aspect of the present invention, a polyphenol surface-modified mesoporous nanoporous microsphere material is provided. The polyphenol surface-modified mesoporous nanoporous microsphere material is prepared by the above preparation method.
[0014] According to a third aspect of the present invention, there is provided an application of a mesoporous nanoporous microsphere material modified with a polyphenolic substance surface for use in the preparation of an anti-tumor drug.
[0015] The advantages and beneficial effects of the present invention are:
[0016] (1) The skeleton of the polyphenol surface modified mesoporous nanoporous microsphere material provided by the present invention is a mesoporous material synthesized from polyphenol (tannic acid and dopamine) and silicon. The polyphenol surface modified mesoporous nanoporous microsphere material has a large number of hydroxyl groups, and a large number of active groups are used to combine with the drug carrier. At the same time, the polyphenol surface modified mesoporous nanoporous microsphere material can interact with manganese or zinc or ferric nitrate solution through electrostatic interaction, so as to further improve the multifunctional properties of the polyphenol surface modified mesoporous nanoporous microsphere material as a bioload material.
[0017] (2) The polyphenol surface-modified mesoporous nanoporous microsphere material provided by the present invention is used to prepare anti-tumor drugs, metal / polyphenol surface-modified mesoporous microspheres, polyphenols and metals form a nanocomposite layer, and the composite layer has strong adhesion and acid responsiveness; a multifunctional nanocomposite material can be formed on the surface of the mesoporous microspheres. On the one hand, polyphenols such as tannic acid act as the "gatekeeper" of the mesoporous channels on the surface of the mesoporous microspheres, playing an effective drug loading function; on the other hand, tannic acid and copper, zinc and iron play an effective Fenton reaction, so this combination can achieve the combination of tumor drug loading and chemodynamic therapy.
[0018] (3) The preparation method of the present invention is simple, and the prepared polyphenol surface-modified mesoporous nanoparticles have uniform particle sizes. The average size of the polyphenol surface-modified mesoporous nanoporous microsphere material is 130 nm, and the pore size is 5.2 nm, showing good drug loading potential. The nanoparticles have an average particle size of 130 nm, are responsive to the tumor microenvironment, and can be effectively enriched in tumor tissues through the EPR effect to achieve drug release and chemodynamic therapy.
[0019] (4) The present invention uses polyphenol-metal with Fenton reaction catalytic activity to modify the surface of mesoporous nanospheres, and constructs polyphenol-metal-mesoporous microspheres with tumor microenvironment responsiveness; under acidic physiological conditions, the metal ligand network will responsively release metal ions, thereby catalyzing endogenous H 2 O 2 Produces -OH. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] Figure 1 This is the TEM spectrum of the Fe-tannic acid surface modified mesoporous microspheres of Example 1.
[0021] Figure 2 This is the TEM spectrum of the Fe-dopamine surface modified mesoporous microspheres of Example 2.
[0022] Figure 3 This is the BET spectrum of the Fe-tannic acid surface modified mesoporous microspheres of Example 1.
[0023] Figure 4 This is the BET spectrum of the Fe-dopamine surface modified mesoporous microspheres of Example 2.
[0024] Figure 5 This is a temperature rise curve of the dispersion of MSN-PTA surface modified with Fe-tannic acid in Example 1 under 808 nm laser. DETAILED DESCRIPTION
[0025] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below through specific implementation methods in conjunction with the accompanying drawings. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.
[0026] Example 1
[0027] The invention provides a method for preparing a polyphenol surface-modified mesoporous nanoporous microsphere material, which specifically comprises the following steps.
[0028] Step 1, add 0.45g CTAB, 35mL ethanol and 150mL deionized water into a flask, and stir continuously for 30min at 70°C to completely dissolve it; first add 12mL ammonia water (wt=25%) into the flask, then add 3.42g tetraethyl orthosilicate dropwise into the mixed solution, after 5min, add 100mg tannic acid, and continue stirring and reacting for 24h; then centrifuge (3000rpm) for 5min, filter, wash with ethanol, and dry at 60°C; finally, reflux extract with 200mL (10mg / mL) ammonium nitrate ethanol solution at 80°C for 24h, repeat the extraction 3 times to obtain MSN-PDA.
[0029] Step 2: Add 20 mL (0.1 mol / L) of ferric nitrate solution to 500 mg of MSN-PDA; stir at 30° C. for 24 h; filter, wash, and dry to obtain MSN-PDA-Fe.
[0030] Example 2
[0031] The invention provides a method for preparing a polyphenol surface-modified mesoporous nanoporous microsphere material, which specifically comprises the following steps.
[0032] Step 1: Add CTAB, anhydrous ethanol and deionized water into a flask in a volume ratio of 0.5:30:100.
[0033] Step 2: Add ammonia water, tetraethyl orthosilicate and dopamine hydrochloride to the micellar solution in a mass ratio of 34:15:0.2, and continue stirring the reaction for 24 hours; then centrifuge (3000 rpm) for 5 minutes, filter, wash with ethanol, and dry at 60°C; finally, reflux extract with 200 mL (10 mg / mL) of ammonium nitrate ethanol solution at 80°C for 24 hours, and repeat the extraction 3 times.
[0034] Step 3: Add 20 mL (0.1 mol / L) of ferric nitrate solution to 500 mg of MSN-PDA; stir at 30° C. for 24 h; filter, wash, and dry to obtain MSN-PDA-Fe.
[0035] The following characterization tests were performed on the MSN-PDA prepared in Example 1 and Example 2, wherein the attached Figure 1 and attached Figure 2 TEM spectra of the Fe-tannic acid surface-modified mesoporous microspheres of Example 1 and TEM spectra of the Fe-dopamine surface-modified mesoporous microspheres of Example 2; Figure 3 and attached Figure 4 Attached are the BET spectra of the Fe-tannic acid surface modified mesoporous microspheres of Example 1 and the BET spectra of the Fe-dopamine surface modified mesoporous microspheres of Example 2; Figure 5 This is a temperature rise curve of the dispersion of MSN-PTA surface modified with Fe-tannic acid in Example 1 under 808 nm laser.
[0036] Obviously, it should be understood by those skilled in the art that the above-mentioned various steps of the present invention can be performed in a manner different from the present invention, and the simulation method and experimental equipment include but are not limited to the above description. The above-mentioned various steps of the present invention can be performed in an order different from that here in some cases, and the steps shown or described above can be performed separately. Therefore, the present invention is not limited to any specific combination of hardware and software.
[0037] The above contents are further detailed descriptions of the present invention in combination with specific implementation methods, and it cannot be determined that the specific implementation of the present invention is limited to these descriptions. For ordinary technicians in the technical field to which the present invention belongs, several simple deductions or substitutions can be made without departing from the concept of the present invention, which should be regarded as falling within the scope of protection of the present invention.
Claims
1. A method for preparing a polyphenol surface-modified mesoporous nanoporous microsphere material, characterized in that: include: (1) Using the co-condensation synthesis method, 0.45 g CTAB, 35 mL anhydrous ethanol and 150 mL deionized water were added to a flask and stirred for 30 min at 70 ° C to completely dissolve them; then 12 mL of ammonia water was added to the flask, and the mass fraction of ammonia water was 25%. Then 3.42 g of tetraethyl orthosilicate was added dropwise to the mixed solution. After 5 minutes, 100 mg of polyphenols were added and the reaction was continued with stirring for 24 hours; (2) Then centrifuge at 3000 rpm for 5 min, filter, wash with ethanol, and dry at 60 °C, and finally extract with 200 mL of 10 mg / mL ammonium nitrate ethanol solution at 80 °C for 24 h, repeat the extraction three times to obtain MSN-PDA; (3) Add 20 mL of manganese solution, zinc solution or ferric nitrate solution to 500 mg of MSN-PDA, stir at 30 °C for 24 h, filter, wash and dry to obtain MSN-PDA-Mn, MSN-PDA-Zn and MSN-PDA-Fe.
2. The method for preparing a polyphenol surface modified mesoporous nanoporous microsphere material according to claim 1, characterized in that: In the step (1), the usage ratio of CTAB, anhydrous ethanol, tetraethyl orthosilicate and polyphenol is 300-450 mg: 35 mL: 12 mL: 3420 mg: 100 mg.
3. The method for preparing a polyphenol surface modified mesoporous nanoporous microsphere material according to claim 1, characterized in that: In the step (1), the polyphenolic substances are tannic acid and dopamine.
4. The method for preparing a polyphenol surface modified mesoporous nanoporous microsphere material according to claim 1, characterized in that: In the step (3), the concentration of the copper solution or zinc solution or ferric nitrate solution is 0.1 mol / L, and the pH value is 6.0-8.
0.
5. A polyphenol surface modified mesoporous nanoporous microsphere material, characterized in that: The polyphenol surface modified mesoporous nanoporous microsphere material is prepared by the preparation method described in any one of claims 1-4.
6. Use of the polyphenol surface modified mesoporous nanoporous microsphere material according to claim 5 in the preparation of anti-tumor drugs.