Preparation method and application of near-infrared two-region photoresponse Bi / BiOI enhanced compound enzyme

Abstract

The invention relates to the field of biological functional materials, and discloses a preparation method and application of a near-infrared two-region photoresponse Bi / BiOI enhanced compound enzyme. The specific method comprises the following steps: firstly, by taking bismuth nitrate pentahydrate as a bismuth source, sodium iodide as an iodine source and ethylene glycol as a reaction solvent, heating and reacting for a period of time to prepare a BiOI nano material; and then the Bi / BiOI compound enzyme is obtained through reduction of sodium borohydride. The compound enzyme is good in crystallinity, is in a spherical shape of 500-700nm, has CAT enzyme activity under tumor microenvironment response, shows excellent self-enhanced enzyme activity under near-infrared second-region light, effectively solves the problem of low activity generally existing in current cancer treatment nano-enzymes, and has application potential in the aspect of CT imaging.

Description

Technical Field

[0001] The present invention relates to the field of biofunctional materials and discloses a preparation method and application of a near-infrared second-region light-responsive Bi / BiOI enhanced composite enzyme, which is used to solve the problem of low enzyme activity caused by hypoxia in the tumor microenvironment during cancer treatment. Background Art

[0002] Cancer has become one of the major threats to human health. Traditional treatments such as surgery, chemotherapy, and radiotherapy have serious limitations. Enzyme therapy is an emerging anti-tumor method. For example, CAT enzyme activity can use hydrogen peroxide in the tumor microenvironment to produce oxygen, alleviating the hypoxia limitation in photodynamic therapy. Compared with traditional therapies, it has the advantages of being minimally invasive, highly selective, highly efficient, and having minimal toxic side effects, and is attracting increasing attention. If the lesion site can be tracked and fed back in real time during the treatment process, it will help improve the efficiency and accuracy of the treatment. Therefore, the development of visualized CAT-enhanced nanozymes is of great significance.

[0003] In recent years, BiOI-based nanomaterials have been widely studied for energy, environmental, and biological applications. The crystal structure of BiOI is composed of alternating layers of [Bi2O2] sheets, halogens, Bi-O, and Bi-I bonds, connected by strong covalent bonds and fragile I-I van der Waals interactions. BiOI exhibits excellent CAT enzyme activity, which can be exploited to enhance therapeutic processes. Furthermore, BiOI can be used as a contrast agent in computed tomography (CT), photoacoustic (PA), and other imaging modalities, providing real-time monitoring and detection guidance.

[0004] Based on the above considerations, the present invention adopts solvothermal method and reduction method to prepare Bi / BiOI enhanced complex enzyme, and explores its CAT enzyme activity and enhanced performance in response to tumor microenvironment and in vitro imaging function, in order to obtain a near-infrared second-region light-enhanced complex enzyme. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention discloses a near-infrared (NIR) light-responsive Bi / BiOI-enhanced composite enzyme. This material exhibits uniform size and excellent dispersibility. Bismuth oxyiodide is reduced with sodium borohydride to form a Bi / BiOI composite structure, significantly enhancing near-infrared light absorption and exhibiting excellent CAT enzyme activity and enhancement performance. Furthermore, this material possesses CT imaging capabilities, demonstrating promising potential for visualization in cancer therapy.

[0006] The present invention is achieved through the following technical solutions: A method for preparing a near-infrared second-region light-responsive Bi / BiOI-enhanced composite enzyme comprises the following steps: (1) adding bismuth nitrate pentahydrate and sodium iodide to ethylene glycol and stirring respectively to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution, adding the sodium iodide solution dropwise to the bismuth nitrate pentahydrate solution and stirring to obtain an orange-red solution, transferring the solution to a reactor and heating the reaction for a period of time, cooling the solution to room temperature after the reaction is completed and centrifuging, washing the solid obtained by centrifugation and vacuum drying to obtain BiOI; (2) Add the BiOI obtained in step (1) into deionized water and stir evenly, add sodium borohydride and stir for a period of time, and obtain the Bi / BiOI enhanced composite enzyme after centrifugation, washing and drying.

[0007] Preferably, the stirring time in step (1) is 30-40 min.

[0008] Preferably, the molar ratio of bismuth nitrate pentahydrate to sodium iodide in step (1) is 1:1.

[0009] Preferably, the solvent thermal reaction conditions in step (1) are a heating temperature of 160° C. to 200° C. and a reaction time of 1 h to 3 h, more preferably a heating temperature of 160° C. and a reaction time of 1 h.

[0010] Preferably, the mass ratio of BiOI:sodium borohydride in step (2) is 20:1.

[0011] Preferably, the stirring time in step (2) is 30-40 min.

[0012] Preferably, the centrifugal speed in step (1) and step (2) is 8000-10000 rpm, and the centrifugal time is 10 min.

[0013] Preferably, the Bi / BiOI porous nanozyme formed in step (2) is spherical with a diameter of about 600 nm.

[0014] Application of the near-infrared second-region light-responsive Bi / BiOI enhanced composite enzyme.

[0015] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0016] (1) The present invention adopts the solvent thermal method and the reduction method to prepare the Bi / BiOI enhanced composite enzyme with uniform size and good dispersibility. The preparation method is simple to operate, the reaction conditions are easy to control, and the feasibility is high.

[0017] (2) The near-infrared second-region light-responsive Bi / BiOI-enhanced composite enzyme described in the present invention has excellent CAT enzyme activity and self-enhancement performance, which solves the defect of low activity caused by hypoxia in the tumor microenvironment during cancer treatment. In addition, it has excellent CT imaging capabilities. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the XRD pattern of the Bi / BiOI enhanced composite enzyme in Example 1.

[0019] Figure 2 This is the SEM image of the Bi / BiOI enhanced composite enzyme in Example 1.

[0020] Figure 3 This is the solid UV-visible-near-infrared absorption spectrum of BiOI and Bi / BiOI enhanced composite enzyme in Example 1.

[0021] Figure 4 This is a graph showing the CAT enzyme activity of the Bi / BiOI enhanced composite enzyme in Example 2.

[0022] Figure 5 This is a graph showing the CAT enzyme activity enhancement performance of the Bi / BiOI enhanced composite enzyme in Example 3 under 1064 nm wavelength laser irradiation.

[0023] Figure 6 This is the CT imaging image of the Bi / BiOI enhanced composite enzyme in Example 4. DETAILED DESCRIPTION

[0024] The present invention will be described in further detail below with reference to the embodiments and the accompanying drawings, but the embodiments of the present invention are not limited thereto.

[0025] Example 1 A method for preparing a near-infrared second-region light-responsive Bi / BiOI-enhanced composite enzyme comprises the following steps: (1) Weigh 1.2125 g of bismuth nitrate pentahydrate and 0.375 g of sodium iodide, add them to 15 mL of ethylene glycol and stir for 30 min to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution, respectively. Add the sodium iodide solution dropwise to the bismuth nitrate pentahydrate solution and stir to obtain an orange-red solution. Then transfer the mixed solution to a stainless steel reactor with a polytetrafluoroethylene liner and seal it. Place the reactor in an oven and keep it at 160°C for 1 hour. After the reaction is completed, cool it to room temperature in the oven. Take out the reaction product and centrifuge it at 8000 rpm for 10 minutes. Wash it with deionized water and anhydrous ethanol three times each. Place the centrifugal precipitate in a vacuum drying oven and dry it at 60°C for 8 hours to obtain BiOI powder. (2) Accurately weigh 100 mg of BiOI and add it to 30 mL of deionized water and stir evenly. Then, add 5 mg of sodium borohydride and stir for 30 min. After the reaction is completed, wash with deionized water and anhydrous ethanol three times each. The centrifuged precipitate is placed in a vacuum drying oven and dried at 60 °C for 8 h to obtain the Bi / BiOI enhanced complex enzyme.

[0026] Figure 1The XRD pattern of the Bi / BiOI enhanced composite enzyme prepared by the solvent thermal method and reduction method in Example 1 is as follows: Figure 1 As shown, the diffraction peaks of the sample are basically consistent with those of the standard PDF card of pure BiOI (JCPDS10-0445) and the standard PDF card of elemental Bi (JCPDS 85-1329). At 2θ=13.58° corresponding to the (0 1 2) crystal plane, Bi in the nanoparticles grows in situ, and the crystallinity of the sample after reduction is high.

[0027] Figure 2 is the SEM image of Bi / BiOI prepared in Example 1, as shown Figure 2 As shown in the figure, Bi / BiOI nanoparticles are spherical with a diameter of about 600 nm, a rough surface and a large number of pores.

[0028] Figure 3 The solid UV-visible-near-infrared absorption spectra of BiOI and Bi / BiOI enhanced composite enzyme in Example 1 clearly show that Bi / BiOI has higher light absorption intensity than BiOI in the near-infrared region.

[0029] Example 2 CAT enzyme activity study Prepare a 0.5 mg / mL Bi / BiOI solution and stir it constantly. Add 1 mM hydrogen peroxide solution to a total volume of 10 mL. Use a dissolved oxygen meter to record the oxygen concentration generated over 10 minutes. Also, establish control groups with deionized water and hydrogen peroxide solution and test the oxygen content under the same conditions.

[0030] Figure 4 The sample's CAT performance demonstrated significant oxygen generation capacity and excellent CAT enzyme activity. The generated oxygen content reached 16.82 mg / L in 10 minutes, effectively alleviating the problem of hypoxia in the tumor microenvironment during treatment.

[0031] Example 3 Study on Enhancement of CAT Enzyme Activity A Bi / BiOI solution with a concentration of 0.5 mg / mL was prepared and stirred at a constant speed. A 1 mM hydrogen peroxide solution was added to a total volume of 10 mL. The oxygen concentration generated within 10 minutes was recorded using a dissolved oxygen meter under 1064 nm laser irradiation.

[0032] Figure 5 The CAT enzyme activity enhancement study of the sample showed that the sample showed stronger CAT enzyme activity under near-infrared light irradiation, and the oxygen content generated in 10 minutes was 19.36 mg / L. This shows that near-infrared light in the second region can enhance the CAT enzyme activity of Bi / BiOI complex enzyme, which can effectively solve the defect of low activity caused by hypoxia in the tumor microenvironment during cancer treatment.

[0033] Example 4 In vitro CT imaging study Bi / BiOI solutions of different concentrations were prepared for CT imaging tests, and the CT imaging of the samples was obtained as follows: Figure 6 As shown, as the concentration increases, the sample imaging becomes clearer and can be used to monitor and guide precise treatment.

Claims

1. Application of a near-infrared second-region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes, characterized in that The preparation method of the Bi / BiOI enhanced complex enzyme comprises the following steps: (1) adding bismuth nitrate pentahydrate and sodium iodide to ethylene glycol and stirring respectively to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution, respectively, adding the sodium iodide solution dropwise to the bismuth nitrate pentahydrate solution and stirring to obtain a red-black solution, transferring the solution to a reactor and heating for reaction, cooling the solution to room temperature after the reaction is completed and centrifuging, washing the solid obtained by centrifugation and vacuum drying to obtain BiOI; (2) Adding the BiOI obtained in step (1) into deionized water, adding sodium borohydride and stirring, and obtaining Bi / BiOI nanomaterials after centrifugation, washing and drying.

2. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The stirring time in step (1) is 30-40 min.

3. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The molar ratio of bismuth nitrate pentahydrate to sodium iodide in step (1) is 1:

1.

4. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The conditions for the solvent thermal reaction in step (1) are a heating temperature of 160° C.-200° C. and a reaction time of 1 h-3 h.

5. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The mass ratio of BiOI:sodium borohydride in step (2) is 20:

1.

6. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The stirring time in step (2) is 30-40 min.

7. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The centrifugal speed in step (1) and step (2) is 8000-10000 rpm, and the centrifugal time is 10 min.

8. The use of a near-infrared second region light-responsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes according to claim 1, characterized in that: The Bi / BiOI nanomaterial formed in step (2) is spherical with a diameter of 500-700 nm.

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