Preparation method and application of near-infrared two-region light response Bi / BiOI enhanced composite enzyme

Abstract

This invention relates to the field of biofunctional materials, and discloses a method for preparing and applying a near-infrared II photoresponsive Bi / BiOI enhanced composite enzyme. Specifically, the method involves first preparing BiOI nanomaterials by heating a reaction mixture of bismuth pentahydrate as the bismuth source, sodium iodide as the iodine source, and ethylene glycol as the reaction solvent for a period of time; then, the Bi / BiOI composite enzyme is obtained by reduction with sodium borohydride. This composite enzyme exhibits good crystallinity, with a spherical morphology of 500-700 nm, and possesses CAT enzyme activity under tumor microenvironment response. Simultaneously, it displays excellent self-enhancing enzyme activity under near-infrared II light, effectively solving the low activity problem commonly found in current cancer therapy nanozymes, and also showing potential application in CT imaging.

Description

Technical Field

[0001] This invention relates to the field of biofunctional materials and discloses a method for preparing and applying a near-infrared II photoresponsive 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 Technology

[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 approach. For example, CAT enzyme activity can utilize hydrogen peroxide in the tumor microenvironment to generate oxygen, alleviating hypoxia limitations in photodynamic therapy. Compared to traditional therapies, it has advantages such as being minimally invasive, highly selective, highly efficient, and having minimal toxic side effects, and is attracting increasing attention. Real-time tracking and feedback of the lesion site during treatment will help improve treatment efficiency and precision. Therefore, the development of visualized CAT-enhanced nanozymes is of great significance.

[0003] In recent years, BiOI-based nanomaterials have been extensively studied in the fields of energy, environment, and biology. The crystal structure of BiOI consists of alternating stacks of [Bi₂O₂] sheets, halogens, Bi-O bonds, and Bi-I bonds, connected by strong covalent bonds and fragile van der Waals interactions between I-I bonds. BiOI possesses excellent CAT enzyme activity, which can be utilized to enhance therapeutic processes. Furthermore, BiOI can also be used as a contrast agent in computed tomography (CT) imaging, photoacoustic (PA) imaging, and other forms of imaging to provide real-time monitoring and detection guidance.

[0004] Based on the above considerations, this invention uses solvothermal and reduction methods to prepare Bi / BiOI enhanced complex enzymes, and explores their CAT enzyme activity and enhancement performance in response to the tumor microenvironment and their in vitro imaging function, in order to obtain a near-infrared II region light-enhanced complex enzyme. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention discloses a near-infrared II photoresponsive Bi / BiOI enhanced composite enzyme. This material exhibits uniform size and good dispersibility. Bismuth iodide is reduced by sodium borohydride to form a Bi / BiOI composite structure, which significantly enhances the light absorption capacity in the near-infrared region, demonstrating excellent CAT enzyme activity and enhancement performance. Furthermore, this material possesses CT imaging capabilities, showing great application potential in the field of visual cancer treatment.

[0006] This invention is achieved through the following technical solution:

[0007] A method for preparing a near-infrared II photoresponsive Bi / BiOI enhanced complex enzyme includes the following steps:

[0008] (1) Bismuth nitrate pentahydrate and sodium iodide were added to ethylene glycol and stirred to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution respectively. Sodium iodide solution was added dropwise to bismuth nitrate pentahydrate solution and stirred to obtain orange-red solution. The solution was transferred to a reaction vessel and heated to react for a period of time. After the reaction was completed, the solution was cooled to room temperature and centrifuged. The solid obtained by centrifugation was washed and vacuum dried to obtain BiOI.

[0009] (2) Add the BiOI obtained in step (1) to deionized water and stir evenly. Add sodium borohydride and stir for a period of time. After centrifugation, washing and drying, the Bi / BiOI enhanced complex enzyme is obtained.

[0010] Preferably, the stirring time in step (1) is 30-40 min.

[0011] Preferably, the molar ratio of bismuth nitrate pentahydrate to sodium iodide in step (1) is 1:1.

[0012] Preferably, the conditions for the solvothermal reaction in step (1) are a heating temperature of 160℃-200℃ and a reaction time of 1h-3h, more preferably a heating temperature of 160℃ and a reaction time of 1h.

[0013] Preferably, the mass ratio of BiOI to sodium borohydride in step (2) is 20:1.

[0014] Preferably, the stirring time in step (2) is 30-40 min.

[0015] Preferably, the centrifugation speed in steps (1) and (2) is 8000-10000 rpm, and the centrifugation time is 10 min.

[0016] Preferably, the Bi / BiOI porous nanozyme formed in step (2) is spherical with a diameter of about 600 nm.

[0017] The application of the near-infrared II photoresponsive Bi / BiOI enhanced complex enzyme.

[0018] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0019] (1) The present invention uses solvothermal method and reduction method to prepare Bi / BiOI enhanced complex enzyme with uniform size and good dispersibility. The preparation method is simple to operate, the reaction conditions are easy to control, and it is highly feasible.

[0020] (2) The near-infrared two-zone photoresponsive Bi / BiOI enhanced complex enzyme described in this invention has excellent CAT enzyme activity and self-enhancing performance, which solves the defect of low activity caused by hypoxia in the tumor microenvironment during cancer treatment. In addition, it also has excellent CT imaging capabilities. Attached Figure Description

[0021] Figure 1 The image shows the XRD pattern of the Bi / BiOI enhanced complex enzyme in Example 1.

[0022] Figure 2 This is a SEM image of the Bi / BiOI enhanced complex enzyme in Example 1.

[0023] Figure 3 The solid UV-Vis-NIR absorption spectra of BiOI and Bi / BiOI enhanced complex enzymes in Example 1 are shown.

[0024] Figure 4 The image shows the CAT enzyme activity of the Bi / BiOI enhanced complex enzyme in Example 2.

[0025] Figure 5 The graph shows the enhanced CAT enzyme activity of the Bi / BiOI enhanced complex enzyme in Example 3 under 1064nm wavelength laser irradiation.

[0026] Figure 6 This is a CT image of the Bi / BiOI enhanced complex enzyme in Example 4. Detailed Implementation

[0027] The present invention will now be described in further detail with reference to the embodiments and accompanying drawings, but the implementation of the present invention is not limited thereto.

[0028] Example 1: A method for preparing a near-infrared II photoresponsive Bi / BiOI enhanced complex enzyme, comprising the following steps:

[0029] (1) Weigh 1.2125g of bismuth nitrate pentahydrate and 0.375g of sodium iodide and add them to 15mL of ethylene glycol and stir for 30min to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution respectively. Add sodium iodide solution dropwise to bismuth nitrate pentahydrate solution and stir to obtain 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℃ for 1h. After the reaction is completed, cool it to room temperature with the furnace. Take out the reaction product and centrifuge at 8000rpm for 10min. Wash it three times each with deionized water and anhydrous ethanol. Place the centrifuged precipitate in a vacuum drying oven and dry it at 60℃ for 8h to obtain BiOI powder.

[0030] (2) Accurately weigh 100 mg of BiOI and add it to 30 mL of deionized water and stir evenly. Add 5 mg of sodium borohydride and stir for 30 min. After the reaction is complete, wash with deionized water and anhydrous ethanol 3 times each. Centrifuge the precipitate and place it in a vacuum drying oven to dry at 60 °C for 8 h to obtain Bi / BiOI enhanced complex enzyme.

[0031] Figure 1 The XRD patterns of the Bi / BiOI enhanced complex enzyme prepared by the solvothermal and reduction methods in Example 1 are shown below. Figure 1 As shown, the diffraction peaks of the sample are basically consistent with those of the standard PDF card (JCPDS10-0445) of pure phase BiOI and the standard PDF card (JCPDS 85-1329) of elemental Bi. At 2θ = 13.58° corresponding to the (0 1 2) crystal plane, Bi in nanoparticles grows in situ, and the crystallinity of the reduced sample is relatively high.

[0032] Figure 2 The image shows a SEM image of the Bi / BiOI prepared in Example 1, as follows. Figure 2 As shown, the Bi / BiOI nanoparticles are spherical with a diameter of about 600 nm, and have a rough surface with a large number of pores.

[0033] Figure 3 The solid UV-Vis-NIR absorption spectra of BiOI and Bi / BiOI enhanced complex enzymes in Example 1 clearly show that Bi / BiOI has a higher light absorption intensity than BiOI in the near-infrared region.

[0034] Example 2: Study on CAT enzyme activity

[0035] A 0.5 mg / mL Bi / BiOI solution was prepared and stirred at a constant speed. A 1 mM hydrogen peroxide solution was added, bringing the total solution volume to 10 mL. The oxygen concentration generated over 10 minutes was recorded using a dissolved oxygen analyzer. A control group of deionized water and hydrogen peroxide solution was established, and oxygen content was tested under the same conditions.

[0036] Figure 4 The sample exhibits excellent CAT enzyme activity and demonstrates significant oxygen generation capacity. The generated oxygen content reaches 16.82 mg / L within 10 minutes, which effectively alleviates the problem of tumor microenvironment hypoxia during treatment.

[0037] Example 3: Study on Enhanced CAT Enzyme Activity

[0038] A Bi / BiOI solution with a concentration of 0.5 mg / mL was prepared and stirred at a constant speed. 1 mM hydrogen peroxide solution was added, and the total volume of the solution was 10 mL. The concentration of oxygen generated within 10 min was recorded using a dissolved oxygen meter under 1064 nm laser irradiation.

[0039] Figure 5 This study investigated the enhancement of CAT enzyme activity in the samples. Under near-infrared light irradiation, the samples exhibited stronger CAT enzyme activity, with an oxygen content of 19.36 mg / L generated within 10 minutes. This indicates that near-infrared II light can enhance the CAT enzyme activity of Bi / BiOI complex enzymes, effectively addressing the deficiency of low activity caused by tumor microenvironment hypoxia during cancer treatment.

[0040] Example 4: In vitro CT imaging study

[0041] Bi / BiOI solutions of different concentrations were prepared for CT imaging tests, and the CT images of the samples were obtained as follows: Figure 6 As shown, the sample imaging becomes clearer with increasing concentration, which can be used to monitor and guide precise treatment.

Claims

1. The application of a near-infrared II photoresponsive Bi / BiOI enhanced composite enzyme in the preparation of cancer therapeutic nanozymes, characterized in that, The Bi / BiOI enhanced complex enzyme was prepared by a method comprising the following steps: (1) Bismuth nitrate pentahydrate and sodium iodide were added to ethylene glycol and stirred for 30-40 min respectively to obtain clear and transparent bismuth nitrate pentahydrate solution and sodium iodide solution respectively; sodium iodide solution was added dropwise to bismuth nitrate pentahydrate solution and stirred to obtain reddish-black solution; the solution was transferred to a reaction vessel and heated at 160℃-200℃ for 1h-3h; after the reaction was completed, the solution was cooled to room temperature and centrifuged at 8000-10000 rpm for 10 min. The solid obtained by centrifugation was washed and vacuum dried to obtain BiOI; The molar ratio of bismuth nitrate pentahydrate to sodium iodide is 1:

1. (2) Add the BiOI obtained in step (1) to deionized water and add sodium borohydride. Stir for 30-40 min and then centrifuge at 8000-10000 rpm for 10 min. After washing and drying, the solid obtained by centrifugation is used to obtain spherical Bi / BiOI nanomaterials with a diameter of 500-700 nm. The mass ratio of BiOI to sodium borohydride is 20:

1. The Bi / BiOI nanomaterials exhibit self-enhanced CAT enzyme activity under near-infrared II light irradiation.

2. The application according to claim 1, characterized in that, The heating temperature of the solvothermal reaction in step (1) is 160°C, and the reaction time is 1 h.

3. The application according to claim 1, characterized in that, The stirring time in step (1) is 30 min.

4. The application according to claim 1, characterized in that, The stirring time in step (2) is 30 min.

5. The application according to claim 1, characterized in that, The centrifugation speed in step (1) and / or step (2) is 8000 rpm and the centrifugation time is 10 min.

6. The application according to claim 1, characterized in that, The diameter of the Bi / BiOI nanomaterial is 600 nm.

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