CN113384699B - Porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione - Google Patents
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Abstract
The invention discloses a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle and a preparation method thereof. The nanoparticle takes nitrosoglutathione, tetra (4-carboxyphenyl) porphyrin in an organic ligand, cobalt nitrate hexahydrate of metal salt and chitosan as basic materials to prepare the porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione. The obtained nano particles have uniform particle size distribution and good biocompatibility. The nanoparticle is an anti-tumor and anti-infection strategy integrating photodynamic therapy, photothermal therapy and gas therapy, can overcome the defect of monotherapy, and has wide application prospect in anti-tumor and anti-infection treatment.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione.
Background
Tumors are a major disease that is harmful to human health, and traditional tumor treatment methods include chemotherapy, radiotherapy and surgical therapies, but have serious side effects or cannot achieve good effects, so exploring treatment methods that have small and effective side effects becomes a research hotspot. Bacterial infection has become one of the major threats to global human health, however the long term and overuse of traditional antibiotics has accelerated the evolution and formation of antibiotic-resistant bacteria. Controlling bacterial infection by means of antibiotics and related methods alone will increase the risk of bacterial resistance. Therefore, developing new strategies that can inhibit and kill bacteria and effectively avoid developing bacterial resistance is a major issue in the current medical health arts.
Photodynamic therapy has been used in clinical cases for the treatment of tumors and is a treatment method that is small in side effects and effective. With the enhancement of drug resistance of drug-resistant bacteria to traditional antibiotics, photodynamic therapy has been attracting attention of researchers because of its unique advantages of non-invasiveness and broad-spectrum anti-infectivity, and the therapeutic mechanism of photodynamic therapy (PDT) is based on super-strong oxidative reaction of Reactive Oxygen Species (ROS) such as hydroxyl radicals, super-oxygen anions, hydrogen peroxide, singlet oxygen, etc. on tumor cells and bacteria. Compared with the conventional anti-tumor and anti-infection treatment methods, PDT has the following advantages: 1) The photoactivation of the photosensitizer can realize controllability through illumination time and position, so that toxic and side effects of the system are minimized; 2) PDT has no specific recognition to treatment cells and bacteria, so that the PDT has broad-spectrum anti-tumor and anti-infective properties; 3) When PDT is applied to the treatment of diseases in organisms, the damage to host cells is small; 4) PDT has the characteristics of safety, reliability and convenience; 5) PDT can be used alone or in combination with other therapeutic methods, including radiation therapy, chemotherapy, photothermal therapy, gene therapy, and immunotherapy.
Photothermal therapy is a noninvasive, controllable, efficient and low-toxicity treatment technology and has great treatment potential for treating tumors and infections. Photothermal therapy is to destroy the protein structure of tumor cells and bacteria by generating local hyperthermia, thereby affecting the normal physiological response and causing irreversible damage to the tumor cells and bacteria. However, the photothermal anti-tumor and anti-infection require higher temperature, which causes thermal damage to normal tissues and limits the clinical application of the photothermal anti-tumor and anti-infection. And are therefore often used in combination with other treatments to reduce the side effects of photothermal therapy.
The gas therapy is a high-efficiency anti-tumor and anti-infection therapy. Among the gas therapies, nitric Oxide (NO) therapy has received widespread attention due to its various anti-tumor, anti-infective mechanisms, and the therapeutic mechanisms of NO therapy include: 1) React with DNA of tumor cells and bacteria and inhibit repair of the DNA to inhibit growth of the tumor cells and bacteria; 2) Reacts with ROS to produce more reactive peroxynitrite ions (ONOO) - ) To enhance the anti-tumor and anti-infection effects.
In order to make up for the defect of monotherapy, a porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione is constructed, and the combination of photodynamic therapy, gas therapy and photothermal therapy can generate ONOO with higher activity than ROS - Realizes the effect of mild photothermal anti-tumor and anti-infection.
Disclosure of Invention
In order to make up the defects of anti-tumor and anti-infection of monotherapy, the invention takes nitrosoglutathione and tetra (4-carboxyphenyl) porphyrin in organic ligand, cobalt nitrate hexahydrate of metal salt and chitosan as basic materials, prepares porphyrin metal organic frame nano-particles by a hydrothermal reaction method, loads nitrosoglutathione as NO donor, wraps the NO donor by chitosan, improves biocompatibility, constructs the nitrosoglutathione-loaded porphyrin metal organic frame nano-particles, and can combine photodynamic therapy, photothermal therapy and gas therapy for anti-tumor and anti-infection.
In order to achieve the above purpose, the invention adopts the following technical scheme:
step 1: dissolving cobalt nitrate hexahydrate and polypyrrolidone in a mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol, dissolving medium tetra (4-carboxyphenyl) porphyrin in a mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol, dropwise adding the medium tetra (4-carboxyphenyl) porphyrin solution into the cobalt nitrate hexahydrate and the polypyrrolidone solution under stirring, carrying out ultrasonic treatment, reacting at 80 ℃, centrifuging, and washing to obtain porphyrin metal organic frame nanoparticles;
step 2: dispersing the porphyrin metal organic frame nanoparticle obtained in the step 1 with water, dissolving nitrosoglutathione with water, dropwise adding the nitrosoglutathione solution under stirring, stirring at room temperature, centrifuging, washing, dispersing the obtained nanoparticle with water, adding the chitosan solution under stirring, stirring at room temperature, centrifuging, washing, and obtaining the nitrosoglutathione-loaded porphyrin metal organic frame nanoparticle.
As a further improvement of the present invention, step 1 is specifically: dissolving 2-6 mg of cobalt nitrate hexahydrate and 20-200 mg of polypyrrolidone in 12-16 mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), dissolving 4mg of tetra (4-carboxyphenyl) porphyrin in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), dropwise adding the tetra (4-carboxyphenyl) porphyrin solution into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, carrying out ultrasonic treatment, reacting at 80 ℃ for 22-28 h, centrifuging, and washing with absolute ethyl alcohol to obtain porphyrin metal organic frame nanoparticles.
As a further improvement of the present invention, step 2 is specifically: dispersing the porphyrin metal organic frame nanoparticle obtained in the step (1) by using 4mL of water, dissolving nitroso glutathione by using 1-4 mL of water, adding the nitroso glutathione solution into porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature for 12-16 hours in a dark place, centrifuging, washing with water, dispersing the obtained nanoparticle by using 4mL of water, adding 0.75-1 mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitroso glutathione-loaded porphyrin metal organic frame nanoparticle.
According to the invention, the porphyrin metal organic framework nanoparticle is prepared by a hydrothermal reaction method, and the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle which is loaded with nitrosoglutathione and wraps chitosan is further successfully prepared.
The invention has the innovation that the invention is an anti-tumor and anti-infection strategy integrating photodynamic therapy, photothermal therapy and gas therapy, makes up the defect of single anti-tumor and anti-infection therapy, generates ROS, NO and RNS and gentle photo-heat under the excitation of a laser, and realizes the combined application of three therapies.
Drawings
FIG. 1 is an external view of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle;
FIG. 2 is a graph showing the particle size distribution of nitrosoglutathione-loaded porphyrin metal organic framework nanoparticles;
FIG. 3 shows the photodynamic performance profile of nitrosoglutathione loaded porphyrin metal organic framework nanoparticles;
FIG. 4 shows the photodynamic properties of nitrosoglutathione loaded porphyrin metal organic framework nanoparticles irradiated for different times;
FIG. 5 photo-thermal effect graph of nitrosoglutathione loaded porphyrin metal organic framework nanoparticles;
FIG. 6 is an in vitro nitric oxide release profile of nitrosoglutathione loaded porphyrin metal organic framework nanoparticles;
FIG. 7 shows the antimicrobial properties of nitrosoglutathione loaded porphyrin metal organic framework nanoparticles;
Detailed Description
The invention is illustrated in further detail by the following examples:
example 1
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 2mg of cobalt nitrate hexahydrate and 20mg of polypyrrolidone are dissolved in 12mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, the mixture is subjected to ultrasonic treatment, the reaction is carried out for 22 hours at 80 ℃, and water and absolute ethyl alcohol are used for washing after centrifugation, so that porphyrin metal organic framework nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 1mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 2
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 20mg of polypyrrolidone are dissolved in 12mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 22 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 1mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 3
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 12mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 22 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 1mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 4
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 16mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 22 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 1mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 5
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 16mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 28 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 1mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 6
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 16mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 28 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 4mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 12h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 7
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 16mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 28 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 4mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 16h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle.
Example 8
The embodiment is a preparation method of a nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle, which comprises the following steps:
(1) 6mg of cobalt nitrate hexahydrate and 200mg of polypyrrolidone are dissolved in 16mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mL of mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol (V: V=3:1), the tetra (4-carboxyphenyl) porphyrin solution is dropwise added into the mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, after ultrasonic treatment is carried out for a few minutes, the mixture is reacted for 28 hours at 80 ℃, and after centrifugation, water and absolute ethyl alcohol are used for washing, so that porphyrin metal organic frame nanoparticles are obtained.
(2) Dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitrosoglutathione with 4mL of water, adding the nitrosoglutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature in a dark place for 16h, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 1mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the nitrosoglutathione-loaded porphyrin metal organic frame nanoparticle.
Example 9
The appearance of the prepared nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle is shown in figure 1
Example 10
And (3) examining the particle size distribution of the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticles by adopting a particle sizer. The porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione is dispersed in water, and the particle size distribution is measured, as shown in figure 2, and the particle size is uniform.
Example 11
Mixing nitrosoglutathione-loaded porphyrin metal organic framework nanoparticles with 1, 3-diphenyl isobenzofuran (DPBF) with a power density of 0.3W/cm 2 The mixed solution of the porphyrin metal organic framework nanoparticles loaded with nitrosoglutathione with different concentrations is irradiated with 660nm laser, and the change of the fluorescence intensity of DPBF is detected by a fluorescence spectrophotometer, as shown in FIG. 3, the lower the fluorescence intensity is with the increase of the concentration, which indicates that the generated active oxygen is increased.
Example 12
Mixing 10 μg/mL of nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle with 1, 3-diphenyl isobenzofuran (DPBF) with a power density of 0.3W/cm 2 The mixed solution of water and DPBF is controlled by irradiating 660nm laser for 5min, and detecting change of DPBF fluorescence intensity by fluorescence spectrophotometer4, the lower the fluorescence intensity, the higher the generated active oxygen.
Example 13
With a power density of 0.3W/cm 2 The laser of 660nm is used for irradiating different concentrations of porphyrin metal organic framework nanoparticle suspension loaded with nitrosoglutathione, and the temperature change in 10min of irradiation is recorded. As shown in FIG. 5, the temperature of the suspension of the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle gradually rises along with the increase of the laser irradiation time, which indicates that the nanoparticle has the photo-thermal conversion performance.
Example 14
And (3) irradiating the suspension of the porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione by using 660nm lasers with different power densities for different times, centrifuging, taking supernatant, and measuring the release amount of nitric oxide by a Griess method. As shown in FIG. 6, the nitrosoglutathione-loaded porphyrin metal organic frame nanoparticle can release nitric oxide under the condition of laser irradiation, and the release amount of nitric oxide gradually increases with the irradiation time.
Example 15
Mixing porphyrin metal organic framework nanoparticles loaded with nitrosoglutathione at different concentrations with bacterial suspension, and using a power density of 0.3W/cm 2 And (3) irradiating the laser for 3min with 660nm laser, measuring OD600 of different groups, and calculating the antibacterial rate of different groups. As shown in FIG. 7, the nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle has higher antibacterial rate at the concentration of 3 mug/mL.
Claims (4)
1. A porphyrin metal organic framework nanoparticle loaded with nitrosoglutathione comprises nitrosoglutathione, tetra (4-carboxyphenyl) porphyrin in an organic ligand, cobalt nitrate hexahydrate of metal salt and chitosan;
the preparation method comprises the following steps:
(1) Dissolving cobalt nitrate hexahydrate and polypyrrolidone in a mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol, dissolving medium tetra (4-carboxyphenyl) porphyrin in a mixed solvent of N, N-dimethylformamide and absolute ethyl alcohol, dropwise adding the medium tetra (4-carboxyphenyl) porphyrin solution into the cobalt nitrate hexahydrate and the polypyrrolidone solution under stirring, carrying out ultrasonic treatment, reacting at 80 ℃, centrifuging, and washing to obtain porphyrin metal organic frame nanoparticles;
(2) Dispersing the porphyrin metal organic frame nanoparticle obtained in the step (1) by using water, dissolving nitrosoglutathione by using water, dropwise adding the nitrosoglutathione solution under stirring, stirring at room temperature, centrifuging, washing, dispersing the obtained nanoparticle by using water, adding the chitosan solution under stirring, stirring at room temperature, centrifuging, and washing to obtain the nitrosoglutathione-loaded porphyrin metal organic frame nanoparticle.
2. The nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle according to claim 1, wherein the preparation step (1) specifically comprises the following steps: dissolving 2-6 mg of cobalt nitrate hexahydrate and 20-200 mg of polypyrrolidone in 12-16 mLN, and the volume ratio of N-dimethylformamide to absolute ethyl alcohol is 3:1, 4mg of tetra (4-carboxyphenyl) porphyrin is dissolved in 4mLN, N-dimethylformamide and absolute ethyl alcohol in a volume ratio of 3:1, dropwise adding a medium tetra (4-carboxyphenyl) porphyrin solution into a mixed solution of cobalt nitrate hexahydrate and polypyrrolidone under stirring, carrying out ultrasonic treatment, reacting at 80 ℃ for 22-28 h, centrifuging, and washing with absolute ethyl alcohol to obtain porphyrin metal organic framework nanoparticles.
3. The nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle according to claim 1, wherein the preparation step (2) specifically comprises the following steps: dispersing the porphyrin nanoparticle obtained in the step (1) with 4mL of water, dissolving nitroso glutathione with 1-4 mL of water, adding the nitroso glutathione solution into the porphyrin nanomaterial dispersion liquid under stirring, stirring at room temperature for 12-16 h in a dark place, centrifuging, washing with water, dispersing the obtained nanoparticle with 4mL of water, adding 0.75-1 mL of 1% chitosan solution under stirring, and reacting at room temperature to obtain the porphyrin metal organic framework nanoparticle loaded with nitroso glutathione.
4. The nitrosoglutathione-loaded porphyrin metal organic framework nanoparticle according to claim 1, which is characterized by being applicable to photodynamic therapy, photothermal therapy and gas therapy in combination with anti-tumor and anti-infection.
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