WO2023130514A1

WO2023130514A1 - Coordination polymer nano material having combined photodynamic-starvation therapy function, preparation method therefor and application thereof

Info

Publication number: WO2023130514A1
Application number: PCT/CN2022/073661
Authority: WO
Inventors: 潘逸航; 许宇智; 曾乐立
Original assignee: 中山大学附属第七医院(深圳)
Priority date: 2022-01-04
Filing date: 2022-01-25
Publication date: 2023-07-13
Also published as: CN114452385A; CN115381944A

Abstract

A coordination polymer nano material having a combined photodynamic-starvation therapy function, a preparation method therefor and an application thereof. The coordination polymer nano material comprises a carrier and an enzyme. The enzyme is loaded in the carrier. The enzyme is glucose oxidase (GOx) or a mimic enzyme having a GOx-like activity. The carrier is a 1,2,4-triazole copper (I) complex. The GOx in the coordination polymer nano material can be specifically released in a tumor cell, and catalyze the oxidation of glucose in the tumor cell, consuming glucose and oxygen in the tumor cell, and improving the levels of acidity, low oxygen and hydrogen peroxide, thereby blocking the energy supply to the tumor cell, and achieving a starvation therapy. Meanwhile, hydrogen peroxide produced by the starvation therapy can also be used as a raw material for a photodynamic reaction of the 1,2,4-triazole copper (I) complex, thereby enhancing the type I photodynamic therapy effect, and finally achieving an efficient combined photodynamic-starvation therapy.

Description

A coordination polymer nanomaterial with photodynamic combined starvation therapy function and its preparation method and application

technical field

The invention belongs to the technical field of nanomaterials, and in particular relates to a coordination polymer nanomaterial with the function of photodynamic combined with starvation therapy and its preparation method and application.

Background technique

Starvation therapy that relies on depleting intratumoral glucose represents an important antitumor therapeutic strategy. Among them, as a biocatalyst, glucose oxidase (Glucose Oxidase; GOx) can effectively consume glucose and oxygen in the tumor microenvironment, and increase the level of acidity, hypoxia and hydrogen peroxide, thereby blocking the energy supply of tumor cells, Enables non-invasive starvation healing. But since other cell types (e.g., immune cells, stem cells) also undergo aerobic glycolysis, glucose-consuming starvation therapeutic strategies often produce severe concurrent toxicity to normal cells. Therefore, it is very important to introduce the design concept of smart nanomaterials in the treatment mode to reduce systemic toxicity while consuming glucose in the tumor with high specificity, which is very important to improve the safety and efficacy of starvation treatment.

Coordination polymers are a class of functional materials that are connected by metal ions and organic ligands through coordination bonds. Due to the structure/function designability, high loading rate, and high biocompatibility of coordination polymers, they are widely used as nanocarriers in bioimaging, tumor therapy, and gene transfection, etc. However, in terms of starvation therapy, there are few types of coordination polymers to choose from, and most of them do not have tumor microenvironment responsiveness and therapeutic properties. It needs to be combined with other drug modifications to achieve the purpose of combined therapy, which increases the drug dose and the resulting damage. Security Question.

Therefore, it is necessary to develop a new coordination polymer nanomaterial with low toxicity, tumor microenvironment responsiveness and therapeutic properties.

Contents of the invention

The present invention aims to solve at least one of the above-mentioned technical problems existing in the prior art. Therefore, the present invention provides a coordination polymer nanomaterial with photodynamic combined starvation therapeutic function.

The invention also provides a preparation method of the coordination polymer nanometer material with photodynamic combined starvation therapy function.

The invention also provides an antitumor drug.

The invention also provides an application of a coordination polymer nanometer material with photodynamic combined starvation therapy function.

The first aspect of the present invention provides a coordination polymer nanomaterial with photodynamic combined starvation therapy function, the coordination polymer material includes a carrier and an enzyme, the enzyme is loaded inside the carrier, the The enzyme is glucose oxidase or a simulated enzyme with glucose oxidase-like activity; the carrier is 1,2,4-triazole copper (I) complex.

The coordination polymer material provided by the present invention includes a carrier and an enzyme. Because the

carrier

1,2,4-triazole copper (I) complex wraps the enzyme, the glucose in the blood cannot enter the interior of the material and the glucose oxidase ( GOx) reaction, inhibiting the reaction between GOx and blood sugar, thereby reducing the systemic toxicity of GOx. Due to the high permeability and retention (EPR) effect of solid tumors, coordination polymer nanomaterials will accumulate in tumor tissues, and after being phagocytized by cancer cells, they will be released under the degradation of glutathione (GSH) highly expressed by cancer cells. Out load GOx. The released GOx catalyzes the oxidation reaction of glucose in cancer cells to form hydrogen peroxide. At the same time, the coordination polymer can catalyze the decomposition of hydrogen peroxide to produce OH under 808nm excitation, and finally achieve the specific effect of photodynamic combined starvation therapy on tumor cells.

One of the technical solutions of the present invention about coordination polymer nanomaterials has at least the following beneficial effects:

The GOx in the coordination polymer nanomaterial of the present invention can be released specifically in tumor cells, can catalyze the oxidation of glucose in tumor cells, consume glucose and oxygen therein, and increase the levels of acidity, hypoxia and hydrogen peroxide , thereby blocking the energy supply of tumor cells and realizing starvation therapy. At the same time, the hydrogen peroxide produced by starvation therapy can become the raw material for the photodynamic reaction of the 1,2,4-triazole copper (I) complex, which enhances the effect of type I photodynamic therapy, and finally realizes efficient photodynamic combined with starvation treat. This method has the following advantages:

(1) The non-porous structure of the nanomaterial forms a protective barrier for starvation therapy, which can reduce the systemic toxicity of GOx without additional drug modification, so that it will not react with blood sugar to produce toxic hydrogen peroxide during the systemic circulation, Greatly increased the safety of starvation healing.

(2) The nanomaterial exhibits excellent cancer cell targeting, can specifically release GOx in tumor cells, and perform tumor cell-specific photodynamic combined starvation therapy without causing toxicity to normal cells. Safe nanocarriers for starvation therapy.

(3) The 1,2,4-triazole copper (I) complex is used as a cell delivery carrier for enzymes for starvation therapy, and as a photosensitizer itself for type I photodynamic therapy of hypoxia tolerance, without binding Other drug modifications can achieve the purpose of combination therapy, reducing drug dosage and achieving efficient combination therapy.

(4) The combination of starvation therapy and type I photodynamic therapy showed high anti-tumor efficacy at the cellular level and animal level, indicating that this multifunctional nanomedicine is expected to be used as a therapeutic platform for starvation therapy and photodynamic synergy. In cancer treatment, it has a good application prospect.

According to some embodiments of the present invention, the enzyme loading in the coordination polymer nanomaterial is 10-30%.

According to some embodiments of the present invention, the 1,2,4-triazole copper (I) belongs to the monoclinic system and the P-1 space group, and the unit cell parameters are:

α=79.648(4)°, β=79.043(3)°, γ=78.855(4)°.

A second aspect of the present invention provides a method for preparing the coordination polymer nanomaterial, comprising the steps of:

The enzyme, Cu ₂ O and 1,2,4-triazole are mixed and reacted, and the coordination polymer nanometer material is obtained through solid-liquid separation.

The coordination polymer nanometer material of the invention can be rapidly produced under mild conditions, ensures no loss of enzyme activity, is simple to prepare, easy to obtain raw materials, and is easy to realize large-scale industrial production.

According to some embodiments of the present invention, the mass ratio of the enzyme, Cu ₂ O and 1,2,4-triazole is 1:(4-8):(3-6).

According to some embodiments of the present invention, the reaction time is 30-60 minutes.

According to some embodiments of the present invention, the reducing agent comprises ascorbic acid or hydrazine hydrate.

According to some embodiments of the present invention, the protective atmosphere includes nitrogen or argon.

According to some embodiments of the present invention, the Cu ₂ O is prepared by the following method: reacting a copper salt under the condition of a reducing agent and an inorganic base to generate Cu ₂ O.

According to some embodiments of the present invention, the inorganic base includes sodium hydroxide or potassium hydroxide.

The third aspect of the present invention provides an anti-tumor drug, which includes the above-mentioned coordination polymer nanomaterial having the function of photodynamic combined starvation therapy.

The fourth aspect of the present invention provides an application of a coordination polymer nanomaterial with photodynamic combined starvation therapy function in the preparation of antitumor drugs.

Description of drawings

Fig. 1 is a schematic diagram of the principle of the present invention;

Fig. 2 is the XRD figure of 1,2,4-triazole copper (I) complex;

Fig. 3 is the result figure of protein electrophoresis;

Fig. 4 is the infrared spectrogram of 1,2,4-triazole copper (I) complex, GOx and embodiment 1 coordination polymer;

Fig. 5 is the SEM figure of 1,2,4-triazole copper (I) complex and embodiment 1 coordination polymer;

Fig. 6 is the enzymatic activity effect figure of GOx, embodiment 1 and comparative example 1 coordination polymer;

Fig. 7 is the comparison diagram of the enzyme activity of the coordination polymer of embodiment 1 before and after ultrasonic;

Fig. 8 is the BET test figure of the coordination polymer of ZIF-8, comparative example 2, 1,2,4-triazole copper (I) complex and the coordination polymer of embodiment 1;

Fig. 9 is the toxicity data graph of 1,2,4-triazole copper (I) complex and Example 1 coordination polymer to MCF-7;

Figure 10 is a graph showing the toxicity data of GOx, the coordination polymers of Example 1 and Comparative Example 2 to cancer cells and normal cells;

Fig. 11 is the fluorescence value of APF after the coordination polymer of embodiment 1 is excited by hydrogen peroxide and 808nm;

Figure 12 is flow cytometry analysis of the cancer cell apoptosis rate of the coordination polymer in Example 1;

Fig. 13 is a graph showing the change of tumor volume over time in different treatment groups.

Detailed ways

The technical solutions in the embodiments of the present invention will be clearly and completely described below, but the implementation manners of the present invention are not limited thereto.

The reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the technical field unless otherwise specified.

The raw materials adopted in the following examples and comparative examples are as follows:

Cancer cells: human breast cancer cell MCF-7 and human bladder cancer cell 5637 were purchased from the Cell Resource Center of Shanghai Institute of Biological Sciences, Chinese Academy of Sciences.

Normal cells: human normal breast epithelial cells MCF-10A were purchased from the Cell Resource Center of Shanghai Institute of Biological Sciences, Chinese Academy of Sciences.

Mice: Female BALB/C nude mice (6-8 weeks) were purchased from the Guangdong Provincial Medical Experimental Animal Center and used with the approval of the Animal Use and Care Committee of Sun Yat-sen University. All animal experiments were carried out in accordance with the National Regulations on the Care and Use of Laboratory Animals.

GOx@ZIF-8 nanoparticles: First, dissolve 1.314g Hmim in 20mL of 50mM HEPES buffer, stir well to dissolve, then add 0.073g Zn(CH ₃ COO) ₂ to the mixed solution, stir at room temperature for half an hour, A milky white suspension was formed, and the product was collected by centrifugation at 12,000 rpm for 3 minutes, washed three times with ultrapure water, and then freeze-dried into powder to obtain ZIF-8 nanoparticles. Adding 10 mg GOx to the reaction solution can obtain GOx@ZIF-8 nanoparticles.

Example 1

Embodiment 1 provides a kind of coordination polymer nanomaterial with photodynamic combined starvation therapy function, coordination polymer nanomaterial comprises 1,2,4-triazole copper (I) ([Cu (tz)]) and Enzyme, the enzyme is loaded inside the copper (I) 1,2,4-triazole. The preparation method is as follows:

Add 0.4 g NaOH to 10 mL solution containing 0.2 mmol Cu(NO ₃ ) ₂ and 0.6 mmol ascorbic acid at room temperature to rapidly generate Cu ₂ O nanoparticles, which are washed after centrifugation. Dissolve the generated _Cu2O nanoparticles in 1 mL of ultrapure water. Under nitrogen protection, this 1 mL Cu ₂ O solution was added to 19 mL aqueous solution containing 10 mg GOx, 4

mmol

1,2,4-triazole and 0.7 mmol ascorbic acid. After stirring and reacting at room temperature for half an hour, the product was collected by centrifugation at 12000rpm for 3 minutes, washed three times with ultrapure water, and then freeze-dried into a powder to obtain a coordination polymer nanomaterial (GOx@[Cu(tz)]). The enzyme loading capacity was 20%.

Example 2

Example 2 provides a coordination polymer nanomaterial with the function of photodynamic combined starvation therapy. The preparation method and raw materials are the same as those in Example 1, the only difference being that the enzyme loading is 10%.

Example 3

Example 3 provides a coordination polymer nanomaterial with the function of photodynamic combined starvation therapy. The preparation method and raw materials are the same as those in Example 1, the only difference being that the enzyme loading is 30%.

Comparative example 1

Comparative Example 1 provides a coordination polymer nanomaterial, the preparation method is the same as that of Example 1, the difference is that 3,5-diethyl-1,2,4-triazole is used instead of 1,2,4 - Triazoles.

Comparative example 2

Comparative Example 1 provides a coordination polymer nanomaterial, the preparation method is the same as in Example 1, the difference is that the commonly used coordination polymer ZIF-8 is used to replace 1,2,4-triazole copper (I) Complexes.

Comparative example 3

Comparative Example 3 provides a coordination polymer nanomaterial, the raw material is the same as that of Example 1, the difference is that the enzyme is adsorbed on the surface of copper (I) 1,2,4-triazole. The preparation method is as follows:

Add 0.4 g NaOH to 10 mL solution containing 0.2 mmol Cu(NO ₃ ) ₂ and 0.6 mmol ascorbic acid at room temperature to rapidly generate Cu ₂ O nanoparticles, which are washed after centrifugation. Dissolve the generated _Cu2O nanoparticles in 1 mL of ultrapure water. Under nitrogen protection, this 1 mL Cu ₂ O solution was added to 19 mL aqueous solution containing 4

mmol

1,2,4-triazole and 0.7 mmol ascorbic acid. The reaction was stirred at room temperature for 1 hour. After the solution turned white, 10 mg GOx was added under nitrogen protection. After mixing for half an hour, the product was collected by centrifugation at 12,000 rpm for 3 minutes, washed with ultrapure water three times, and freeze-dried into a powder for later use.

Performance Testing

Fig. 1 is a schematic diagram of the principle of the present invention, including a schematic diagram of the preparation of coordination polymer nanomaterials and a schematic diagram of the principle of the coordination polymer nanomaterials for photodynamic combined starvation therapy of tumor cells.

1. Carry out X-ray diffraction (XRD) on 1,2,4-triazole copper (I) complex, as shown in Figure 2, 1,2,4-triazole copper (I) complex belongs to monoclinic Crystal system, P-1 space group, unit cell parameters are:

α=79.648(4)°, β=79.043(3)°, γ=78.855(4)°.

2. Carry out protein electrophoresis test to 1,2,4-triazole copper (I), the coordination polymer of embodiment 1 and the coordination polymer of comparative example 3:

5 mg of 1,2,4-triazole copper(I), the coordination polymer of Comparative Example 3 or the coordination polymer of Example 1 were reacted with 10 mM GSH for one hour to degrade the material and release GOx into the solution. GOx molecules in the supernatant were detected by protein electrophoresis. As shown in Figure 3, the 1,2,4-triazole copper (I) without enzyme (lane 2) did not have any protein bands. And the coordination polymer of comparative example 3 (swimming lane 3) and the coordination polymer sample (swimming lane 4) of embodiment 1 all can observe the band that has similar position with GOx (swimming lane 1), but the coordination of comparative example 3 The band of the position polymer is shallower than that of the coordination polymer of Example 1, this is because the GOx adsorbed on the surface is easily removed by cleaning, which is not conducive to practical application. On the other hand, the in-situ package has a large loading capacity, is stable, and is not easy to leak, and GOx can only be released under the degradation of GSH.

3. 1,2,4-triazole copper (I), the coordination polymer of embodiment 1 and glucose oxidase are carried out infrared spectrum test:

From Figure 4, both GOx and the coordination polymer of Example 1 have characteristic peaks at 1640-1660 cm- ¹ , corresponding to protein amide I stretching vibration (mainly from C=O stretching), while at 1, 2, There is no such stretching vibration in the 4-triazole copper (I) sample, which further verifies the existence of GOx in the coordination polymer of Example 1.

4. The coordination polymer of 1,2,4-triazole copper (I), embodiment 1 is carried out scanning electron microscopy test:

The scanning electron microscope (SEM) image of Figure 5 shows that 1,2,4-triazole copper (I) is in the form of multi-rod aggregation, which tends to grow anisotropically. However, the coordination polymer in Example 1 tends to grow isotropically and is spherical particles with uneven surface. Dynamic light scattering (DLS) results show that the average particle diameters of 1,2,4-triazole copper (I) and the coordination polymer of Example 1 are about 200nm and 234nm respectively, indicating that the composite material after encapsulating the enzyme The particle size becomes larger.

5. GOx, the coordination polymer nanomaterial of embodiment 1 and the coordination polymer nanometer of comparative example 1 are tested for enzyme activity:

Enzyme activity on glucose: 0.15 μg GOx ^or 50 μg of the coordination polymer of Example 1 was added to 100 μL of PBS buffer ( ^0.01 M, pH 7.4). The real-time change of the absorbance at 415nm was detected with a multifunctional microplate reader, and the enzyme kinetic parameters were calculated by the Michaelis-Menten equation (Fig. 6). The catalytic activity of the coordination polymer nanomaterial obtained in Example 1 is only 1/10000～1/1000 of GOx, and the enzyme catalytic activity of the coordination polymer in Example 1 (k _cat /K _m =0.051s ^-1 mM ⁻¹ ). This is because the non-porous structure of 1,2,4-triazole copper (I) hinders the contact and reaction between GOx and glucose substrate, which can effectively inhibit the activity of GOx. However, when the 1,2,4-triazole copper(I) structure was destroyed (sonication was used here), the enzymatic activity of GOx was restored (Fig. 7).

However, the catalytic activity of the coordination polymer in Comparative Example 1 (k _cat /K _m =240s ^-1 mM ^-1 ) was very high, which was close to that of free GOx (420s ^-1 mM ^-1 ). This is because the coordination polymer in Comparative Example 1 is a porous material and does not have the ability to inhibit the activity of glucose oxidase.

6. The coordination polymer of ZIF-8, comparative example 2, 1,2,4-triazole copper (I) and the coordination polymer of embodiment 1 carry out BET test:

As shown in Figure 8, the nitrogen adsorption data shows that ZIF-8, the coordination polymer of Comparative Example 2, 1,2,4-triazole copper (I) and the coordination polymer of Example 1 are respectively 1360, 888, 67.5 and 27.6m ² g ^-1 , therefore, the coordination polymer of Comparative Example 2 is a porous material and cannot effectively protect enzymes, while the coordination polymer of the present invention has a non-porous structure.

7. The cytotoxicity of 1,2,4-triazole copper (I) and the coordination polymer nanomaterial of Example 1 to human breast cancer cell MCF-7 was determined by MTT method.

As shown in Figure 9, after 24 hours of incubation with 1,2,4-triazole copper (I) in the concentration range of 10-100 μg mL ^-1 , the cell survival rate was above 80%, while 40 μg mL ^-1 of Example 1 The cytotoxicity of coordination polymer nanomaterials is greater than 75%. The results indicated that the composites loaded with GOx showed high cytotoxicity, which has the effect of starvation therapy.

8. Test the coordination polymer nanomaterial of Example 1 and the coordination polymer nanomaterial of Comparative Example 2 for tumor cell specificity:

It is reported in the literature that the concentration of GSH in cancer cells is 3-10 times that of normal cells, and the coordination polymer nanomaterial in Example 1 has the performance of GSH responsive release, so cancer cell-specific starvation therapy can be realized. The cytotoxicity of the coordination polymer nanomaterial in Example 1 to human breast cancer cell MCF-7 and human normal breast epithelial cell MCF-10A was determined by MTT method. As shown in FIG. 10 , the coordination polymer nanomaterial of Example 1 has stronger cytotoxicity to cancer cell MCF-7, showing cancer cell-specific starvation therapeutic effect. However, free GOx and the coordination polymer material of Comparative Example 2 have strong cytotoxicity to cancer cells and normal cells, and have no selectivity. And it cannot be applied, the results show that the coordination polymer nanomaterial of Example 1 can improve the selectivity and safety of starvation treatment.

9. Detect whether the coordination polymer nanomaterial of embodiment 1 has photosensitivity:

APF fluorescein can selectively react with OH to generate fluorescence. PBS solutions of coordination polymer nanomaterials with different concentrations in Example 1 were mixed with 1mM hydrogen peroxide and 0.8mM APF solution, and the solution was irradiated with 808nm laser (1W cm ^-1 ) for 10min. The results in Figure 11 show that the fluorescence intensity of APF increases with the implementation The concentration of the coordination polymer nanomaterial in Example 1 increases and increases, indicating that the coordination polymer nanomaterial in Example 1 can be used as a photosensitizer to generate active oxygen·OH.

Experimental example 1

(1) Photodynamic combined starvation therapy for cancer cells: Human bladder cancer cell line 5637 was divided into six groups, namely (a) control group (PBS), (b) light group (808nm excitation), (c) 1, 2,4-triazole copper (I), (d) single photodynamic therapy group (1,2,4-triazole copper (I)+808nm), (e) single starvation therapy group (embodiment 1) , (f) combined treatment group (embodiment 1+808nm). For the combined treatment group, after incubating 5637 cells with 50 μg mL ^-1 of the coordination polymer of Example 1 for 4 hours, they were irradiated with 808nm laser (0.6W cm ^-1 ) for 20 minutes (two irradiations, 10 minutes each time, with an interval of 5 minutes in between) , and then placed in an incubator to continue culturing for 20 hours. After the culture was over, flow cytometry was used to detect the apoptosis and necrosis of 5637 cells. Early apoptotic cells were only stained by FITC (Q3), and late apoptotic or necrotic cells were stained by both FITC and PI (Q2). Apoptotic rate (Q2+Q3) result is shown in Figure 12, and the apoptotic rate of six groups is respectively 11.21%, 11.11%, 14.28%, 17.32%, 27.98% and 71.69%, and the result shows that combined treatment group compares There is a potentiation effect in the monotherapy groups (d and e), demonstrating the efficacy of combined photodynamic and starvation therapy in tumors.

(2) Photodynamic combined with starvation therapy for tumor-bearing mice: 1×10 ⁷ 5637 cell suspension was subcutaneously injected into the hind legs of female athymic nude mice (six weeks) to construct a 5637 tumor-bearing nude mouse model, which was divided into five groups. Groups, respectively (a) PBS, (b) 1,2,4-triazole copper (I), (c) single photodynamic therapy group (1,2,4-triazole copper (I)+808nm ), (d) single starvation treatment group (Example 1), (e) combined treatment group (Example 1+808nm). Treatment experiments were performed when the tumor volume reached 100 mm ³ . The concentration of nanomaterials is 10 mg kg ^-1 . The light conditions were 24 hours after tail vein injection of drugs, irradiated with 808nm laser (0.6W cm ^-1 ) for 20 minutes (irradiated twice, 10 minutes each time, 5 minutes apart). Figure 13 shows the change of tumor volume over time in different treatment groups. The results showed that the monotherapy groups (c and d) were able to inhibit tumor growth, and the combination therapy group (e) was significantly better than the monotherapy groups (c and d) and the control group (a and b). The combined effect of tumor photodynamic and starvation therapy at the in vivo level was demonstrated.

Embodiment 2 and Embodiment 3 of the present invention have similar effects to Embodiment 1.

Apparently, the above-mentioned embodiments of the present invention are only examples for clearly illustrating the present invention, rather than limiting the implementation of the present invention. For those of ordinary skill in the art, on the basis of the above description, other changes or changes in different forms can also be made. It is not necessary and impossible to exhaustively list all the implementation manners here. All modifications, equivalent replacements and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the claims of the present invention.

Claims

A coordination polymer nanomaterial with photodynamic combined starvation therapy function, characterized in that the coordination polymer nanomaterial includes a carrier and an enzyme, the enzyme is loaded inside the carrier, and the enzyme is glucose Oxidase or mimic enzyme with glucose oxidase-like activity; the carrier is 1,2,4-triazole copper (I) complex.
The coordination polymer nanomaterial with photodynamic combined starvation therapy function according to claim 1, characterized in that the enzyme loading in the coordination polymer nanomaterial is 10-30%.
The coordination polymer nanomaterial with photodynamic combined starvation therapy function according to claim 1, characterized in that, the 1,2,4-triazole copper (I) complex belongs to the monoclinic crystal system, P- 1 space group, the unit cell parameters are:

α=79.648(4)°, β=79.043(3)°, γ=78.855(4)°.
According to any one of claims 1 to 3, the preparation method of the coordination polymer nanomaterial with photodynamic combined starvation therapy function, is characterized in that it comprises the following steps:

Under a protective atmosphere and a reducing agent, the enzyme, Cu 2 O and 1,2,4-triazole are mixed and reacted, and the coordination polymer nanomaterial is obtained through solid-liquid separation.
According to claim 4, the preparation method of the coordination polymer nanomaterial having photodynamic combined starvation therapy function, is characterized in that, the mass ratio of the enzyme, Cu2O and 1,2,4-triazole is 1 : (4~8): (3~6).
According to the preparation method of the coordination polymer nanomaterial with photodynamic combined starvation therapy function according to claim 4, it is characterized in that the reaction time is 30-60 minutes.
According to the preparation method of the coordination polymer nanomaterial with photodynamic combined starvation therapy function according to claim 4, it is characterized in that the reducing agent comprises ascorbic acid or hydrazine hydrate.
According to the preparation method of the coordination polymer nanomaterial with photodynamic combined starvation therapy function according to claim 4, it is characterized in that the protective atmosphere includes nitrogen or argon.
An anti-tumor drug, characterized in that the anti-tumor drug comprises the coordination polymer nanomaterial having the function of photodynamic combined starvation therapy according to any one of claims 1-3.
According to any one of claims 1 to 3, the application of the coordination polymer nanomaterial with photodynamic combined starvation therapy function in the preparation of antitumor drugs.