CN-117180425-B - Near infrared two-region light response metal molybdenum-based nano enzyme, preparation method and application

Abstract

The invention provides a near infrared two-region light response metal molybdenum-based nano enzyme, a preparation method and application thereof, which are characterized in that Mesoporous Silica (MSNs) is used as a template, and metal molybdenum elements are doped in MSNs nanospheres through a calcination method and a metal-acid treatment strategy to obtain HMMSNs@HA nanospheres. Among other things, MSNs effectively control the morphology of small-sized materials due to their unique pore space. HA modification greatly increases its tumor targeting and biocompatibility. The hydrogenation process can endow the nano-enzyme with the capability of stably acting in the tumor microenvironment and rapidly degrading in the physiological environment by penetrating electrons in metal Mo and protons in acid into metal molybdenum oxide in a hydrogen-doped form, and endow the nano-enzyme with an unusual metal-like electronic structure, so that the molybdenum-based nano-enzyme has excellent near infrared two-region light absorption, photo-thermal conversion and photo-responsive oxidase-like activity, namely, generates superoxide anion free radicals under 1064nm laser irradiation to remove cancer cells.

Inventors

• XU JIATING
• FU YUJIE
• LIU MENGTING
• LIU SHUANG
• WANG JIKUN
• ShangGuan Hang
• YE JIN
• ZHANG ZHIYONG
• NIU NA
• CHEN LIGANG

Assignees

• 东北林业大学

Dates

Publication Date

20260512

Application Date

20230609

Claims (5)

1. 1. The preparation method of the near infrared two-region light response metal molybdenum-based nano enzyme is characterized by comprising the following steps of: S1, preparing mesoporous silica supported molybdenum oxide, namely dispersing mesoporous silica MSNs in an organic solvent, respectively adding urea, ammonium chloride mixed solution and acetylacetone molybdenum solution, stirring, drying at 40-60 ℃ to obtain solid, calcining the solid to obtain mesoporous silica supported molybdenum oxide, and marking as MMSNs; S2, preparing mesoporous silica loaded metal-like molybdenum oxide, wherein MMSNs of the mesoporous silica loaded metal-like molybdenum oxide is dispersed in an acidic solution, metal zinc powder is added for reaction to obtain a black product, and the black product is separated, washed and dried to obtain mesoporous silica loaded metal-like molybdenum oxide, which is recorded as HMMSNs; S3, adopting hyaluronic acid HA for modification, namely adopting an organic solvent to respectively dissolve HMMSNs and hyaluronic acid HA to obtain HMMSNs organic solution and hyaluronic acid HA organic solution, mixing the HMMSNs organic solution and the hyaluronic acid HA organic solution, stirring for 10-14 h, separating, washing and drying to obtain metal molybdenum-based nano enzyme, and marking the metal molybdenum-based nano enzyme as HMMSNs@HA; Step S1, the method also comprises the step of synthesizing mesoporous silica nanospheres with good dispersibility and uniform particle size by taking tetraethyl orthosilicate as a silicon source; the step S1 specifically comprises the following steps: Dispersing 25-40 mg of MSNs in absolute ethyl alcohol, adding a mixed solution of urea and ammonium chloride dissolved in water and absolute ethyl alcohol into the solution, adding 0.3-0.4 g of molybdenum acetylacetonate dissolved in 20-30 mL of absolute ethyl alcohol into the solution, fully stirring the obtained mixed solution, and then drying the solvent in an oven at 40-60 ℃ overnight; the step S2 specifically comprises the following steps: Uniformly dispersing 0.1-0.2 g of prepared MMSNs powder into 20-30 mL of hydrochloric acid solution with the concentration of 3-5M, then rapidly adding 0.1-0.2 g of metal zinc powder at the rotation speed of 500-700 rpm for reaction to obtain a black product, centrifugally separating, washing 3-5 times by adopting deionized water and absolute ethyl alcohol, and drying in a vacuum oven at the temperature of 40-60 ℃ for 10-14h; The step S3 specifically comprises the following steps: Firstly, dissolving the synthesized HMMSNs in absolute ethyl alcohol, then dissolving HA in absolute ethyl alcohol, after the HA and the HA are fully dissolved, mixing the HA and the HA, placing the mixture under 40-60 ℃ magnetic stirring for 10-14 hours, centrifuging after reaction, washing and collecting the mixture by deionized water and absolute ethyl alcohol, placing the final product in an oven, and drying the final product under 40-60 ℃ for 10-14 hours to obtain HMMSNs@HA; HMMSNs to HA mass ratio is 1:1-1:2.
2. 2. The preparation method of the near infrared two-region light response type metal molybdenum-based nano enzyme, which is characterized in that a mixed solution of urea and ammonium chloride dissolved in water and absolute ethyl alcohol is prepared by dissolving 2-3 g of urea and 0.5-0.6 g of ammonium chloride in 5-10 mL of water and 10-20 mL of absolute ethyl alcohol.
3. 3. The method for preparing near infrared two-region light response metal-like molybdenum-based nano enzyme according to claim 1, wherein the method further comprises the step of preparing mesoporous silica before the step S1, and specifically comprises the following steps: Firstly, mixing 0.8-1.5 g of cetyl trimethyl ammonium paratoluenesulfonate CTA.tos, 0.1-0.15 g of triethanolamine and 8-15 mg of 1-butyl 3-methyl-imidazole trifluoro methanesulfonate in deionized water, stirring the obtained mixed solution for 1-2 hours at 80-100 ℃, adding 7-8 mL of tetraethyl orthosilicate, continuously stirring at 80-100 ℃ for reacting for 2-3 hours, centrifugally separating and washing the obtained product, removing a template, removing the template CTA.tos, dispersing the centrifugally washed product in absolute ethyl alcohol, stirring and soaking for 20-24 hours, centrifuging for 5-10 minutes, washing twice with absolute ethyl alcohol, and finally transferring the product to a 40-60 ℃ oven for drying, wherein the obtained white powder is MSNs.
4. 4. A near infrared two-region light-responsive metallomolybdenum-based nanoenzyme prepared by the preparation method of any one of claims 1-3.
5. 5. The use of a near infrared two-region light-responsive metal-like molybdenum-based nanoenzyme in the preparation of a drug carrier of claim 4.

Description

Near infrared two-region light response metal molybdenum-based nano enzyme, preparation method and application Technical Field The invention relates to the technical field of nano-enzyme preparation, in particular to a near infrared two-region light response metal molybdenum-based nano-enzyme, a preparation method and application. Background With the rapid development of therapeutic nanomedicine, nanomaterials can be designed to respond to specific stimuli, including endogenous stimuli such as low pH, hypoxia, etc., as well as external physical stimuli such as temperature, light, magnetic fields, and ultrasound, to achieve tumor-specific therapies. Among them, molybdenum (Mo) is used as a nontoxic, low-cost transition metal for developing a photo-responsive nanomaterial having various physicochemical properties to realize various functions. The molybdenum-based nano-drug not only provides effective catalytic sites or polyvalent elements, but also exhibits excellent light-responsive therapeutic functions under laser irradiation. Near Infrared (NIR) laser induced photothermal therapy and photodynamic therapy are two major phototherapy approaches. However, most nanomaterials face a problem that they do not accumulate selectively at the lesions, but interfere with normal tissue affecting treatment. In addition, even if NIR-II light can be effectively absorbed, few photothermal or photosensitizer nanomaterials can produce active oxygen through NIR-II to achieve high photothermal conversion efficiency or excellent photocatalytic performance. Therefore, research and development of a near infrared two-region light-responsive biodegradable metal-like molybdenum-based nano-enzyme have important research significance in the field of biological medicine, and a scheme or a route of the nano-enzyme has not been reported yet. Disclosure of Invention In order to solve the technical problem, one possible method for solving the problem is to hydrogenate the metal molybdenum oxide nano-material loaded in the MSNs mesopores by using Mesoporous Silica (MSNs) as a template through a metal-acid treatment strategy, and realize biological response degradation in a hydrogen doping mode, and meanwhile, the metal-like electronic structure obtained in the hydrogenation process endows the nano-material with metal-like efficient NIR-II light absorption, photo-thermal conversion and photocatalysis performance. In addition, the reasonable surface modification of Hyaluronic Acid (HA) by anticancer nano-enzyme can improve the selective retention of the Hyaluronic Acid (HA) at the tumor site by enhancing the permeability and retention effect of the hyaluronic acid. The invention provides a near infrared two-region light response metal molybdenum-based nano enzyme, a preparation method and application thereof, thereby solving the problems in the prior art. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: In a first aspect, the invention provides a preparation method of near infrared two-region light response metal molybdenum-based nano enzyme, which comprises the following steps: S1, preparing mesoporous silica supported molybdenum oxide, namely dispersing mesoporous silica MSNs in an organic solvent, respectively adding urea, ammonium chloride mixed solution and acetylacetone molybdenum solution, stirring, drying at 40-60 ℃ to obtain solid, calcining the solid to obtain mesoporous silica supported molybdenum oxide, and marking as MMSNs; S2, preparing mesoporous silica loaded metal-like molybdenum oxide, wherein MMSNs of the mesoporous silica loaded metal-like molybdenum oxide is dispersed in an acidic solution, metal zinc powder is added for reaction to obtain a black product, and the black product is separated, washed and dried to obtain mesoporous silica loaded metal-like molybdenum oxide, which is recorded as HMMSNs; and S3, modifying by adopting hyaluronic acid HA, namely fully dissolving HMMSNs and HA respectively by adopting an organic solvent, mixing the two, stirring for 10-14 hours, separating, washing and drying to obtain molybdenum-based nano-enzyme, and marking the molybdenum-based nano-enzyme as HMMSNs@HA. Preferably, the step S1 specifically comprises dispersing 25-40 mg of MSNs in absolute ethyl alcohol, adding a mixed solution of urea and ammonium chloride dissolved in water and absolute ethyl alcohol into the solution, adding 0.3-0.4 g of molybdenum acetylacetonate dissolved in 20-30 mL of absolute ethyl alcohol into the solution, fully stirring the obtained mixed solution, drying the solvent in an oven at 40-60 ℃ overnight, grinding the dried solid, and then carrying out gradient heating calcination in a muffle furnace at a final temperature of 400 ℃ for 4-6 h to obtain MMSNs. Preferably, the mixed solution of urea and ammonium chloride dissolved in water and absolute ethyl alcohol is prepared by dissolving 2-3 g of urea and 0.5-0.6 g of ammonium chloride in 5-10 mL of water