Preparation method of copper-based heterojunction nano material with excellent chemical power treatment effect

Abstract

The invention discloses a preparation method of a copper-based heterojunction nano-material with an excellent chemical kinetics treatment effect, which is a novel nano-material based on synthesis of inorganic chemistry, and efficient inhibition on tumors is realized by using excellent catalytic performance of the copper-based heterojunction nano-material. The synthesis of the nano heterojunction mainly comprises two processes of room temperature reaction and hydrothermal reaction. The specific preparation method comprises the following steps: 1) mixing and stirring copper chloride and ammonium metavanadate at room temperature to form a mixture; 2) centrifuging the obtained mixture; and (3) finally, re-dispersing the precipitate obtained by centrifugation into a mixed solvent of ethylene glycol and water, putting into a high-pressure reaction kettle, reacting for a certain time at a specific temperature, centrifuging, washing, drying and the like to finally obtain the heterojunction nano material of the copper-vanadium bimetallic oxide. The nano material has excellent peroxidase activity, good biocompatibility and biological safety, and an excellent tumor treatment effect.

Description

Technical Field

[0001] The present invention relates to the field of nanobiomaterials, and specifically to the preparation and use of copper-based heterojunction nanomaterials with chemodynamic therapy effects. Background Art

[0002] Cancer poses a major threat to global health, causing millions of deaths every year and showing an upward trend. Traditional cancer treatment methods, such as surgery, chemotherapy (CT), and radiotherapy (RT), are usually limited by their respective side effects. Therefore, in recent years, more and more innovative treatment methods have been developed to avoid the corresponding problems, including chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and starvation therapy (ST). Among them, CDT, as a treatment method that eliminates tumor cells by generating intracellular reactive oxygen species (ROS), has attracted extensive attention due to its unique mechanism triggered by intracellular chemical reactions and significant treatment efficiency. As is well known, the tumor microenvironment (TME) plays an important role in tumor progression. Different from normal tissues, the typical characteristics of TME include hypoxia, acidity, and elevated ROS levels. It is worth noting that excessive H 2 O 2 can be converted into highly cytotoxic hydroxyl radicals (·OH) through the classical Fenton-like reaction during the CDT process, thereby causing devastating damage to cancer cells. As a non-invasive treatment, high tumor specificity and low side effects are the advantages of CDT compared with other treatment methods. Although many progresses have been made in improving the efficiency of CDT in vivo by developing multifunctional nanomaterials with Fenton-like activity, there are still several key problems, including low endogenous H2O2 levels, reduced Fenton-like reaction efficiency at weak acidic pH values of 5.6 - 6.8, and high concentrations of reducing thiol species (such as glutathione GSH). Therefore, developing new CDT nanodrugs to address these limitations has become the focus of research.

[0003] With the rapid development of nanotechnology, nanomaterials with enzyme-like activities, also known as nanozymes, are widely regarded as more suitable alternatives to natural enzymes in the fields of catalysis, environmental protection, and disease treatment. The emergence of nanozymes has revolutionary significance, as it can overcome the inherent disadvantages of natural enzymes, including high cost, poor stability, and complex storage problems. The unique physicochemical properties and excellent catalytic activity of nanozymes make them an ideal option when natural enzymes are not the best choice. In recent years, a large number of nanomaterials with various enzyme activities have been developed, mainly redox-mimicking enzymes. Among the numerous redox-mimicking enzymes, nanomaterials with peroxidase (POD)-like activity have shown great potential in tumor treatment. H 2 O 2It can be rapidly converted into various reactive oxygen intermediates by nanozymes with POD-like activity, including ·OH, 1 O 2 and O 2 ·- , which can effectively kill tumor cells, making them excellent candidates for chemodynamic therapy (CDT). Due to their simpler and cheaper synthesis methods and great application potential, in recent years, more and more nanozymes with peroxidase-like activity have been reported as suitable substitutes for natural peroxidases, such as noble metal nanoparticles (Au NPs, Pt NPs, Ru NPs), carbon-based nanomaterials (graphene oxide, carbon nanotubes, etc.), and metal oxide-based nanomaterials (MxOy, M = iron, cobalt, copper, vanadium, etc.). Among them, transition metal-based nanozymes have attracted extensive attention in the field of disease treatment, especially in cancer treatment. Transition metals have unoccupied d or f orbitals and are easy to coordinate with substrate molecules, which reduces the reaction activation energy for the formation of transition states in catalytic reactions, thus significantly increasing their reaction rates. This property is further reflected in the lattice structure of transition metals, making the corresponding nanozymes have superior electron transfer ability and photothermal conversion efficiency, which play key roles in the treatment results of radiotherapy (RT), photothermal therapy (PTT), chemodynamic therapy (CDT), and other treatment methods. In addition, transition metal-based nanozymes can achieve rapid and large aggregation at the tumor site through responsive or targeted modification strategies, and this effect is very beneficial for their biomedical applications. However, the reported POD-like catalytic activities of currently reported transition metal-based nanozymes are generally not high, and they cannot exhibit more excellent catalytic behaviors and treatment effects. Therefore, there is an urgent need to develop new transition metal-based nanozymes with higher catalytic activities and more precise treatment effects. Summary of the Invention

[0004] Aiming at the problems of low catalytic efficiency of nanozymes and poor chemodynamic therapy effects at present, the present invention aims to synthesize a nanomaterial with excellent chemodynamic therapy effects, make full use of the excessive hydrogen peroxide generated by the tumor microenvironment, and then achieve efficient killing of tumors.

[0005] The technical solution of the present invention is as follows: A preparation method of a copper-based heterojunction nanomaterial with chemodynamic therapy effects, characterized by mainly including the following steps: (1) Preparation of a metal ion coprecipitation mixture: First, copper dichloride dihydrate and ammonium metavanadate are added to a certain volume of deionized water at a certain molar ratio and stirred evenly; then an appropriate amount of hydrochloric acid is added to adjust the pH of the solution system to 6.0, and the reaction is continued to stir at room temperature for 1 h. After the reaction is completed, the precipitate is obtained by centrifugation; (2) Redisperse the precipitate obtained in Step 1 into a mixed solvent system of ethylene glycol and water, stir well until a homogeneous solution is formed, then transfer it to a high-pressure reaction kettle for hydrothermal reaction at 180 °C for 12 h. After the reaction is completed, wait for the temperature of the reaction kettle to drop to room temperature, then centrifuge the obtained material, wash it three times with ethanol and water respectively, and finally dry it at 60 °C to obtain the final material.

[0006] Further, the molar concentration ratio of ammonium metavanadate to copper chloride dihydrate in Step (1) is 1:1 - 5.

[0007] Further, the concentration of the hydrochloric acid solution in Step (1) is 1 mol / L.

[0008] Further, the volume ratio of ethylene glycol to water in Step (2) is 1:1 - 3.

[0009] The main advantages of the present invention are as follows: Aiming at the problems of low catalytic activity of current nanomaterials and poor chemodynamic therapy effects, etc., the present invention has successfully prepared a copper-based heterojunction nanomaterial with excellent chemodynamic therapy effects by reasonably and controllably adjusting the reaction conditions. This nanomaterial not only has very good dispersibility, but also exhibits very high peroxidase-like activity, can efficiently catalyze hydrogen peroxide to generate high-concentration hydroxyl radicals, and can effectively consume glutathione. In addition, this material also has good biocompatibility and safety, and exhibits very excellent tumor suppression effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] In order to make the objectives, technical solutions and beneficial effects of the present invention clearer, the present invention provides the following drawings:

[0011] Figure 1 It is a schematic diagram of the synthesis and action of the copper-based heterojunction nanomaterial with chemodynamic therapy effects in Example 1 of the present invention.

[0012] Figure 2 It is a TEM image of the copper-based heterojunction nanomaterial with chemodynamic therapy effects in Example 1 of the present invention.

[0013] Figure 3 It is an electron paramagnetic resonance spectrum of the copper-based heterojunction nanomaterial with chemodynamic therapy effects in Example 1 of the present invention catalyzing hydrogen peroxide to generate hydroxyl radicals.

[0014] Figure 4 It is an ultraviolet spectrum of the copper-based heterojunction nanomaterial with chemodynamic therapy effects in Example 1 of the present invention consuming glutathione.

[0015] Figure 5In vitro toxicity graph of the copper-based heterojunction nanomaterial with chemodynamic therapy effect on L929 normal cells in Example 1 of the present invention.

[0016] Figure 6 In vitro toxicity graph of the copper-based heterojunction nanomaterial with chemodynamic therapy effect on 4T1 cells in Example 1 of the present invention.

[0017] Figure 7 In vivo antitumor effect graph of the copper-based heterojunction nanomaterial with chemodynamic therapy effect in Example 1 of the present invention. Detailed implementation manners

[0018] The following examples are used to illustrate the present invention, but are not used to limit the scope of the present invention.

[0019] Example 1

[0020] (1) First, 54.5 mg of copper chloride dihydrate and 9.3 mg of ammonium metavanadate were added to 18 mL of deionized water and stirred evenly, where the molar concentration ratio of copper chloride dihydrate to ammonium metavanadate was 4:1; then an appropriate amount of hydrochloric acid was added to adjust the pH of the solution system to 6.0, and the reaction was continued to stir at room temperature for 30 minutes. After the reaction ended, precipitation was obtained by centrifugation.

[0021] (2) The precipitate obtained in step (1) was redispersed in a mixed solvent system of ethylene glycol and water (the total volume of the solution was 30 mL), stirred thoroughly until a homogeneous solution was formed, and then transferred to a high-pressure reaction kettle for hydrothermal reaction at 180 °C for 12 h. After the reaction ended, when the temperature of the reaction kettle dropped to room temperature, the obtained material was centrifuged, washed three times with ethanol and water respectively, and finally dried at 60 °C to obtain the final material.

[0022] Its transmission electron microscope (TEM) is shown in Figure 2 , and the TEM results show that the nanoparticles present a spindle-shaped band structure. Figure 3 is the electron paramagnetic resonance spectrogram of the nanomaterial catalyzing hydrogen peroxide to generate hydroxyl radicals. It can be seen from the figure that the material has an obvious effect of catalyzing hydrogen peroxide to generate hydroxyl radicals. Figure 4 Time-gradient ultraviolet spectrogram of the nanomaterial for glutathione consumption. Glutathione shows a very obvious consumption. Figure 5 and Figure 6 are the in vitro toxicity effects of the material on normal cells L929 and tumor cells 4T1 respectively. The results show that the material has no obvious toxicity to normal cells, but has an obvious inhibition on tumor cell proliferation in the presence of hydrogen peroxide. Figure 7It is the tumor inhibition effect diagram of the nanomaterial in mice under different treatments. It can be seen from the figure that the CVO group shows obvious tumor inhibition effect compared with other groups.

[0023] Finally, it should be noted that the above preferred embodiments are only used to illustrate the technical solutions of the present invention rather than to limit them. Although the present invention has been described in detail through the above preferred embodiments, those skilled in the art should understand that various changes can be made in form and details without departing from the scope defined by the claims of the present invention.

Claims

1. A method for preparing a copper-based heterojunction nanomaterial having a chemodynamic therapeutic effect, mainly comprising the following steps: (1) Preparation of metal ion co-precipitation mixture: First, add copper chloride dihydrate and ammonium metavanadate in a certain molar ratio into a certain volume of deionized water and stir evenly; then add an appropriate amount of hydrochloric acid to adjust the pH of the solution system to 6.0, continue stirring at room temperature for 1 h, and centrifuge to obtain a precipitate after the reaction is completed; (2) The precipitate obtained in step 1 was redispersed in a mixed solvent system of ethylene glycol and water, and stirred thoroughly to form a uniform solution. The solution was then transferred to a high-pressure reactor for hydrothermal reaction at 180 °C for 12 h. After the reaction was completed, the temperature of the reactor was lowered to room temperature, the obtained material was centrifuged, and washed three times with ethanol and water respectively, and finally dried at 60 °C to obtain the final material.

2. The method for preparing the copper-based heterojunction nanomaterial with excellent chemodynamic therapeutic effect according to claim 1, characterized in that: The concentration of the hydrochloric acid solution in step (1) is 1 mol / L.

3. The method for preparing the copper-based heterojunction nanomaterial with excellent chemodynamic therapeutic effect according to claim 1, characterized in that: In the step (1), the molar concentration ratio of ammonium metavanadate to cupric chloride dihydrate is 1:1-5.

4. The method for preparing the copper-based heterojunction nanomaterial with excellent chemodynamic therapeutic effect according to claim 1, characterized in that: In the step (2), the volume ratio of ethylene glycol to water is 1:1-3.

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