A copper-nitroimidazole complex, its preparation method and application
By using copper-nitroimidazole complexes to consume NADPH and GSH in hypoxic tumor cells, a chemokinetic therapy with enhanced GSH metabolism is achieved, solving the problem of high cost of existing composite nanosystems and improving anti-tumor efficacy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- CHANGCHUN INSTITUTE OF APPLIED CHEMISTRY CHINESE ACADEMY OF SCIENCES
- Filing Date
- 2023-08-28
- Publication Date
- 2026-05-29
AI Technical Summary
In current cancer treatments, the composite nanosystems of sorafenib loaded with a porous framework synthesized from zinc ions and 2-nitroimidazole contain multiple components, which increases costs. Meanwhile, methods targeting glutathione (GSH) metabolism have failed to effectively reduce GSH content to enhance anti-tumor effects.
A copper-nitroimidazole complex is formed by the coordination self-assembly of copper ions and 2-nitroimidazole. Under hypoxic conditions, 2-nitroimidazole consumes NADPH to inhibit GSH synthesis, while copper ions consume GSH and enhance the Fenton reaction to generate reactive oxygen species, thus achieving chemokinetic therapy with enhanced GSH metabolism.
This complex consists of only two components and can act selectively in tumor cells, increasing the loading of 2-nitroimidazole, enhancing GSH consumption, inducing ferroptosis, and improving antitumor effects.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of coordination technology, and particularly relates to a copper-nitroimidazole complex, its preparation method and application. Background Technology
[0002] High levels of glutathione (GSH) (2-10 mM) are a crucial component of the antioxidant system in tumor cells, scavenging excess reactive oxygen species (ROS) and maintaining intracellular redox balance. Reducing intracellular GSH levels can disrupt cellular redox homeostasis, leading to ROS accumulation and ultimately causing cell damage and even death, thus hindering the efficacy of anti-tumor therapy. Therefore, targeting GSH metabolism has become an important adjuvant approach to cancer treatment.
[0003] Reducing GSH levels can be achieved by decreasing GSH synthesis and consumption. For example, Li et al. (Conzyme-depleting nanocarriers for enhanced redox cancer therapy under hypoxia) synthesized a porous framework using zinc ions and 2-nitroimidazole, loaded sorafenib, and coated it with an iron-gallic acid complex. This system induces cell death by reducing intracellular GSH and increasing intracellular ROS. However, this composite nanosystem contains many components, increasing its cost. Summary of the Invention
[0004] In view of this, the purpose of the present invention is to provide a copper-nitroimidazole complex, its preparation method and application, wherein the complex contains only copper ions and 2-nitroimidazole, and the simple two-component combination can achieve chemokinetic therapy with enhanced GSH metabolism and induce ferroptosis.
[0005] This invention provides a copper-nitroimidazole complex, which is formed by the coordination and self-assembly of copper ions and 2-nitroimidazole.
[0006] In this invention, 2-nitroimidazole is a hypoxia-responsive drug that exerts its effects only in hypoxic tumor cells, possessing the function of consuming intracellular NADPH and thus inhibiting GSH synthesis. Furthermore, its unique imidazole group allows it to coordinate with metal ions, thereby acquiring additional metal ion functionality.
[0007] The copper ions exhibit excellent Fenton reactivity and GSH consumption capacity.
[0008] In this invention, the molar ratio of the divalent copper ions to 2-nitroimidazole is (4.4-5.0):(4.2-4.7).
[0009] This invention combines copper ions and 2-nitroimidazole, which has the potential to achieve chemokinetic therapy that enhances GSH metabolism and induces ferroptosis.
[0010] In this invention, the size of the copper-nitroimidazole complex is 100 nm to 3 μm, preferably 100 nm to 1 μm, more preferably 100 nm to 500 nm, and most preferably 100 nm to 200 nm.
[0011] This invention provides a method for preparing the copper-nitroimidazole complex described in the above technical solution, comprising the following steps:
[0012] A 2-nitroimidazole solution was added dropwise to a solution containing divalent copper ions, and a regulator was added. The mixture then self-assembled to obtain a copper-nitroimidazole complex.
[0013] In this invention, the regulator is selected from one or more of triethylamine, diethylamine, and dimethylamine. This invention allows for the control of the morphology and size of copper-nitroimidazole by controlling the type and amount of the regulator.
[0014] The solution containing divalent copper ions is one or more of copper nitrate trihydrate solution, copper chloride solution, and copper acetate solution. The concentration of the solution containing divalent copper ions is 0.02–0.3 mol / L.
[0015] The solvent in the solution containing divalent copper ions is an organic solvent or water; the organic solvent is selected from one or more of N,N-dimethylformamide, acetonitrile, anhydrous ethanol, acetone and anhydrous methanol.
[0016] The solvent in the 2-nitroimidazole solution is N,N-dimethylformamide. The concentration of the 2-nitroimidazole solution is 0.016–0.066 mol / L.
[0017] In a specific embodiment of the present invention, preferably, 7.4 mg of copper nitrate trihydrate (Cu(NO3)2·3H2O) is dissolved in an organic solvent or 0-1.5 mL of deionized water, and 3.7 mg of 2-nitroimidazole is dissolved in 0.5-2 mL of N,N-dimethylformamide. Under stirring conditions, the 2-nitroimidazole solution is added dropwise to the Cu(NO3)2·3H2O solution, and then 0.1 mL of triethylamine aqueous solution (0.07 mol / L) is added.
[0018] 2-Nitroimidazole first undergoes deprotonation in a solvent before it can coordinate with divalent copper ions to form crystal nuclei and continue growing. During this process, the deprotonation of 2-nitroimidazole affects the nucleation rate and thus the particle size. In this invention, the central nitrogen atom of triethylamine, acting as the regulator, possesses a lone pair of electrons and can accept protons from 2-nitroimidazole. Water, as a benign ion, can also accept protons. Therefore, when triethylamine is used as the regulator and water is used as the solvent in the solution containing divalent copper ions, both triethylamine and water molecules can increase the deprotonation rate of 2-nitroimidazole, thereby controlling the yield of copper-nitroimidazole nanomedicines with sizes ranging from approximately 100 nm to 800 nm.
[0019] In this invention, the molar ratio of the 2-nitroimidazole, the divalent copper compound in the solution containing divalent copper ions, and the regulator is (4.4-5.0):(4.2-4.7):1.
[0020] In this invention, the 2-nitroimidazole solution is preferably added dropwise to a solution containing divalent copper ions under stirring conditions; the stirring rate is preferably 700-800 rpm.
[0021] In this invention, the self-assembly temperature is room temperature, preferably 10-35°C, and the self-assembly time is 8-10 minutes.
[0022] The present invention also provides an antitumor nanomedicine, comprising the copper-nitroimidazole complex described in the above technical solution or the copper-nitroimidazole complex prepared by the preparation method described in the above technical solution.
[0023] Nanomedicines release copper ions and 2-nitroimidazole in tumor cells. Under hypoxic conditions, 2-nitroimidazole consumes NADPH, thus inhibiting GSH synthesis. Copper ions also consume GSH. This GSH consumption enhances the synthesis of copper ions. 2+ / Cu + Reactive oxygen species generated by the Fenton-mediated reaction.
[0024] This invention provides a copper-nitroimidazole complex, which is self-assembled by coordination of copper ions and 2-nitroimidazole. This complex contains only copper ions and 2-nitroimidazole; this simple two-component combination enables chemokinetic therapy with enhanced GSH metabolism and induces ferroptosis. As a nanomedicine, the copper-nitroimidazole complex exhibits both GSH-responsive and hypoxia-responsive properties, and can selectively act on tumor cells. The nanomedicine releases copper ions and 2-nitroimidazole into tumor cells. Under hypoxic conditions, 2-nitroimidazole consumes reduced nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting GSH synthesis; copper ions also consume GSH. This GSH consumption enhances the chemokinetic effect of copper ions and 2-nitroimidazole. 2+ / Cu +Reactive oxygen species generated by the Fenton-mediated reaction. 2-Nitroimidazole self-assembles with copper ions to form nanomedicines, greatly increasing the loading of 2-nitroimidazole (up to 84.74%). The simple two-component combination achieves chemokinetic therapy with enhanced GSH metabolism and induces ferroptosis. Attached Figure Description
[0025] Figure 1 SEM image of the copper-nitroimidazole complex prepared in Example 1 of this invention;
[0026] Figure 2 SEM image of the copper-nitroimidazole complex prepared in Example 2 of this invention;
[0027] Figure 3 SEM image of the copper-nitroimidazole complex prepared in Example 3 of this invention;
[0028] Figure 4 SEM image of the copper-nitroimidazole complex prepared in Example 4 of this invention;
[0029] Figure 5 SEM image of the copper-nitroimidazole complex prepared in Example 5 of this invention;
[0030] Figure 6 SEM image of the copper-nitroimidazole complex prepared in Example 6 of this invention;
[0031] Figure 7 SEM image of the copper-nitroimidazole complex prepared in Example 7 of this invention;
[0032] Figure 8 SEM image of the copper-nitroimidazole complex prepared in Example 8 of this invention;
[0033] Figure 9 SEM image of the copper-nitroimidazole complex prepared in Example 9 of this invention;
[0034] Figure 10 SEM image of the copper-nitroimidazole complex prepared in Example 10 of this invention;
[0035] Figure 11 SEM image of the copper-nitroimidazole complex prepared in Example 11 of this invention;
[0036] Figure 12 SEM image of the copper-nitroimidazole complex prepared in Example 12 of this invention;
[0037] Figure 13 SEM image of the copper-nitroimidazole complex prepared in Example 13 of this invention;
[0038] Figure 14 SEM image of the copper-nitroimidazole complex prepared in Example 14 of this invention;
[0039] Figure 15 SEM image of the copper-nitroimidazole complex prepared in Example 15 of this invention;
[0040] Figure 16 The cytotoxicity of Cu-NI NPs under normoxic and hypoxic conditions;
[0041] Figure 17 To detect reactive oxygen species in 4T1 cells under different treatments;
[0042] Figure 18 The relative content of GSH in cells under different treatments;
[0043] Figure 19 Transmission electron microscopy images of 4T1 cells under different treatments; the red arrows indicate mitochondria. Detailed Implementation
[0044] To further illustrate the present invention, the following detailed description, in conjunction with embodiments, provides a copper-nitroimidazole complex, its preparation method, and its applications. However, these descriptions should not be construed as limiting the scope of protection of the present invention.
[0045] Example 1:
[0046] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 1 mL of N,N-dimethylformamide, and 3.7 mg 2-nitroimidazole (2-NI) was dissolved in 1 mL of N,N-dimethylformamide. Under stirring, 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 1 μm.
[0047] Example 2:
[0048] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 1 mL acetonitrile, and 3.7 mg 2-nitroimidazole was dissolved in 1 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 3 μm.
[0049] Example 3:
[0050] At room temperature, 7.4 mg of Cu(NO3)2·3H2O was dissolved in 1 mL of anhydrous ethanol, and 3.7 mg of 2-nitroimidazole was dissolved in 1 mL of N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 600 nm.
[0051] Example 4:
[0052] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 1 mL of acetone, and 3.7 mg 2-nitroimidazole was dissolved in 1 mL of N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 800 nm.
[0053] Example 5:
[0054] At room temperature, 7.4 mg of Cu(NO3)2·3H2O was dissolved in 1 mL of deionized water, and 3.7 mg of 2-nitroimidazole was dissolved in 1 mL of N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 300 nm.
[0055] Example 6:
[0056] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 1 mL of anhydrous methanol, and 3.7 mg 2-nitroimidazole was dissolved in 1 mL of N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 500 nm.
[0057] Example 7:
[0058] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 0.1 mL H2O, and 3.7 mg 2-nitroimidazole was dissolved in 1.9 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 800 nm.
[0059] Example 8:
[0060] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 0.3 mL H2O, and 3.7 mg 2-nitroimidazole was dissolved in 1.7 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 500 nm.
[0061] Example 9:
[0062] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 0.5 mL H2O, and 3.7 mg 2-nitroimidazole was dissolved in 1.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 400 nm.
[0063] Example 10:
[0064] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 0.7 mL H2O, and 3.7 mg 2-nitroimidazole was dissolved in 1.3 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 400 nm.
[0065] Example 11:
[0066] At room temperature, 7.4 mg Cu(NO3)2·3H2O was dissolved in 1.5 mL H2O, and 3.7 mg 2-nitroimidazole was dissolved in 0.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 100 nm.
[0067] Example 12
[0068] At room temperature, 0.031 mmol CuCl₂ was dissolved in 1.5 mL H₂O, and 0.033 mmol 2-nitroimidazole was dissolved in 0.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the CuCl₂ solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 200 nm.
[0069] Example 13:
[0070] At room temperature, 0.031 mmol Cu(CH3COO)2·H2O was dissolved in 1.5 mL H2O, and 0.033 mmol 2-nitroimidazole was dissolved in 0.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the CuCl2 solution, followed by 0.1 mL of triethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 100 nm.
[0071] Example 14:
[0072] At room temperature, 0.031 mmol Cu(NO3)2·3H2O was dissolved in 1.5 mL H2O, and 0.033 mmol 2-nitroimidazole was dissolved in 0.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of dimethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 500 nm.
[0073] Example 15:
[0074] At room temperature, 0.031 mmol Cu(NO3)2·3H2O was dissolved in 1.5 mL H2O, and 0.033 mmol 2-nitroimidazole was dissolved in 0.5 mL N,N-dimethylformamide. Under stirring, the 2-nitroimidazole solution was added dropwise to the Cu(NO3)2·3H2O solution, followed by 0.1 mL of diethylamine aqueous solution (0.07 M). The reaction was carried out at room temperature for 10 min. The precipitate was collected by centrifugation to obtain the copper-nitroimidazole complex with a size of approximately 400 nm.
[0075] The components of the copper-nitroimidazole complexes in Examples 1-15 are shown in Table 1:
[0076] Table 1
[0077] Group <![CDATA[Cu 2+ Content (wt%) 2-NI content (wt%) Example 1 20.92 79.08 Example 2 23.95 76.05 Example 3 22.21 77.79 Example 4 19.87 80.13 Example 5 23.31 76.69 Example 6 22.6 77.4 Example 7 15.26 84.74 Example 8 20.73 79.27 Example 9 22.67 77.33 Example 10 23.42 76.58 Example 11 22.35 77.65 Example 12 20.75 79.25 Example 13 23.08 76.92 Example 14 22.37 77.63 Example 15 22.57 77.43
[0078] This invention uses the copper-nitroimidazole nanomedicine (Cu-NI NPs) from Example 11 as an antitumor nanomedicine, and its antitumor effect is characterized as follows:
[0079] MTT assay for cytotoxicity: 4T1 cells were seeded at a density of 8000 cells / well in 96-well plates and incubated overnight under normoxic and anaerobic conditions, respectively. Then, different concentrations of Cu-NI NPs (0–50 μg / mL) were added, and incubation was performed for 24 h under normoxic and anaerobic conditions, respectively. Finally, cell viability was determined using the MTT assay. The results are shown below. Figure 16 As shown, the results indicate that the cytotoxicity of Cu-NI NPs increases with increasing concentration, and the antitumor effect of Cu-NI is more pronounced under hypoxic conditions.
[0080] Intracellular reactive oxygen species (ROS) detection: 4T1 cells were seeded in 6-well plates at a density of 150,000 cells per well and incubated overnight. Then, the cells were treated with PBS, Cu(NO3)2·3H2O, 2-nitroimidazole (2-NI), and Cu-NI NPs (50 μg / mL) for 4 h. The original culture medium was removed, and the cells were soaked in DCFH-DA staining solution for 20 min. Intracellular green fluorescence intensity characterized ROS production. The strongest green fluorescence was observed in the Cu-NI NPs group under an inverted fluorescence microscope (see [link to relevant documentation]). Figure 17 This indicates that Cu(NO3)2·3H2O or 2-NI alone cannot disrupt the intracellular redox balance system, and Cu-NI NPs with synergistic effects exhibit a state of oxidative stress.
[0081] Intracellular glutathione content: 4T1 cells at a density of 2 million cells / cell were placed in 10cm cell culture dishes and cultured for 12 h under normoxic and anaerobic conditions. Then, the cells were co-cultured with PBS, Cu(NO3)2·3H2O, 2-NI, and Cu-NI NPs (50 μg / mL) under normoxic and anaerobic conditions for 12 h, respectively. Subsequently, adherent and floating cells from each group were collected, and intracellular glutathione content was measured using a reduced glutathione assay kit. See [link to details]. Figure 18 The results showed that both copper ions and 2-NI could reduce intracellular GSH levels, and Cu-NI NPs decreased because of Cu 2+ It exhibits stronger GSH depletion capacity through synergistic effects with 2-NI, and cells treated under hypoxic conditions show enhanced GSH depletion.
[0082] Electron microscopy: 4T1 cells were seeded in cell culture dishes and cultured overnight. Then, the cells were treated with PBS, Cu(NO3)2·3H2O, 2-NI, and Cu-NI NPs (50 μg / mL) for 12 h. Cells from each group were collected and fixed with electron microscopy fixative. The mitochondria within the 4T1 cells were observed using transmission electron microscopy. (See also...) Figure 19 The results showed that the Cu-NI NPs-treated group of cells exhibited characteristics of ferroptosis, with smaller mitochondria and increased membrane density.
[0083] As shown in the above embodiments, this invention provides a copper-nitroimidazole complex, which is self-assembled by coordination of copper ions and 2-nitroimidazole. This complex contains only copper ions and 2-nitroimidazole; this simple two-component combination can achieve chemokinetic therapy with enhanced GSH metabolism and induce ferroptosis. The copper-nitroimidazole complex, as a nanomedicine, exhibits both GSH-responsive and hypoxia-responsive properties, and can selectively act on tumor cells. The nanomedicine releases copper ions and 2-nitroimidazole in tumor cells. Under hypoxic conditions, 2-nitroimidazole consumes NADPH, thereby inhibiting GSH synthesis, while copper ions similarly consume GSH. The consumption of GSH enhances the chemokine metabolism of copper ions and 2-nitroimidazole. 2+ / Cu + Reactive oxygen species generated by the Fenton-mediated reaction. 2-Nitroimidazole self-assembles with copper ions to form nanomedicines, greatly increasing the loading of 2-nitroimidazole (up to 84.74%). The simple two-component combination achieves chemokinetic therapy with enhanced GSH metabolism and induces ferroptosis.
[0084] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A copper-nitroimidazole complex, which is formed by the coordination self-assembly of divalent copper ions and 2-nitroimidazole; The preparation method of the copper-nitroimidazole complex includes the following steps: A copper-nitroimidazole complex was obtained by adding a 2-nitroimidazole solution dropwise to a solution containing divalent copper ions and adding a regulator. The regulator is triethylamine.
2. The copper-nitroimidazole complex according to claim 1, characterized in that, The molar ratio of the divalent copper ions to 2-nitroimidazole is (4.4~5.0):(4.2~4.7).
3. The copper-nitroimidazole complex according to claim 1, characterized in that, The size of the copper-nitroimidazole complex is 100 nm to 3 μm.
4. A method for preparing the copper-nitroimidazole complex according to any one of claims 1 to 3, comprising the following steps: A copper-nitroimidazole complex was obtained by adding a 2-nitroimidazole solution dropwise to a solution containing divalent copper ions and adding a regulator. The regulator is triethylamine.
5. The preparation method according to claim 4, characterized in that, The solvent in the solution containing divalent copper ions is one or more of N,N-dimethylformamide, acetonitrile, anhydrous ethanol, acetone, deionized water, and anhydrous methanol. The solvent in the 2-nitroimidazole solution is N,N-dimethylformamide.
6. The preparation method according to claim 4, characterized in that, The solution containing divalent copper ions is one or more of copper nitrate trihydrate solution, copper chloride solution, and copper acetate solution.
7. The preparation method according to claim 4, characterized in that, The molar ratio of the 2-nitroimidazole, the divalent copper compound in the solution containing divalent copper ions, and the regulator is (4.4~5.0):(4.2~4.7):
1.
8. The preparation method according to claim 4, characterized in that, The self-assembly temperature is 10~35℃, and the self-assembly time is 8~10min.
9. An antitumor nanomedicine comprising the copper-nitroimidazole complex according to any one of claims 1 to 3 or the copper-nitroimidazole complex prepared by the preparation method according to any one of claims 4 to 8.