Iron / copper-porphyrin nanoparticles, preparation method and application thereof

By preparing iron/copper-porphyrin nanoparticles, the problem of poor catalytic effect of porphyrin-based nanomaterials was solved, and efficient PDT/CDT combined therapy was achieved in the tumor microenvironment. Through iron/copper ion catalysis and photodynamic reaction, the tumor treatment effect was significantly improved.

CN118005643BActive Publication Date: 2025-12-05LINYI UNIVERSITY
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Patent Information

Application Number
CN202410134371.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2024-01-31
Publication Date
2025-12-05
Estimated Expiration
2044-01-31

AI Technical Summary

Technical Problem

Existing porphyrin-based metal-organic framework nanomaterials exhibit poor catalytic performance in tumor microenvironments and consume large amounts of glutathione, resulting in unsatisfactory tumor treatment outcomes.

Method used

Iron/copper-porphyrin nanoparticles were synthesized via a solvothermal method. They exhibited uniform particle size and good stability, and contained iron and copper ions. These nanoparticles were able to efficiently catalyze the Fenton reaction and photodynamic reaction in the tumor microenvironment, releasing hydroxyl radicals and singlet oxygen.

Benefits of technology

It improves the efficacy of tumor treatment by consuming glutathione, promoting the accumulation of hydroxyl radicals and singlet oxygen, and achieving the combined therapeutic effect of PDT/CDT.

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Abstract

The application discloses an iron / copper-porphyrin nanoparticle and a preparation method and application thereof, and the nanoparticle is prepared through the following steps: adding iron chloride, copper chloride, tetra(4-carboxyphenyl)porphyrin and benzoic acid into a reaction solvent N,N-dimethylformamide solution, uniformly stirring at room temperature, and reacting at high temperature; and after the reaction is completed, the iron / manganese-porphyrin nanoparticle is obtained through centrifugation and washing. The iron / manganese-porphyrin nanoparticle is prepared by using a brand-new method, the nanoparticle can be degraded in a glutathione solution and release iron ions and copper ions, is used for catalyzing hydrogen peroxide to be converted into a hydroxyl radical (•OH), and tetra(4-carboxyphenyl)porphyrin can generate singlet oxygen (O2) under 660 nm laser irradiation, and is expected to become a good nano-carrier for accelerating photodynamic therapy-chemical kinetic therapy. 1 O2).
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Description

Technical Field

[0001] This invention belongs to the field of functional materials preparation technology, specifically relating to an iron / copper-porphyrin nanoparticle, its preparation method, and its application. Background Technology

[0002] In recent years, photosensitizer-based nanoscale metal-organic frameworks (nMOFs), composed of metal ions or metal clusters coordinated with organic bridging ligands, have attracted much attention due to their variable number of metal ions, diverse structures, and large specific surface area. Based on these advantages, nMOFs have found wide application in drug delivery, TME regulation, and cancer therapy. Among them, porphyrin-based nMOFs, with their high photosensitizer loading, easy diffusion of singlet oxygen, and avoidable self-quenching of porphyrin fluorescence, are widely used in photodynamic therapy (PDT) for tumors. Furthermore, the metal ions or metal clusters used in nMOFs can be catalytically active iron or copper ions. These ions can utilize the reducing properties of glutathione to undergo valence state transformation, thereby converting hydrogen peroxide into hydroxyl radicals via the Fenton reaction or Fenton-like reactions. This process can be used in chemodynamic therapy (CDT) for tumors.

[0003] Although porphyrin-based nMOFs can be used in combination with phototherapy (PDT) and tumor catalysis (CDT) to improve tumor treatment efficacy, the abundant reducing agent glutathione in the tumor microenvironment leads to the consumption of singlet oxygen and hydroxyl radicals generated by PDT and CDT. Furthermore, the catalytic effect of single metal ions or metal clusters in porphyrin-based nMOFs is poor. Therefore, maximizing the antitumor efficiency of porphyrin-based nMOFs is a popular trend. Thus, how to improve the catalytic effect of porphyrin-based nMOFs while significantly reducing the glutathione content in tumor sites, thereby improving tumor treatment efficacy, is an urgent problem to be solved. Summary of the Invention

[0004] This invention addresses the problem of poor catalytic effect in existing technologies, which prevents the achievement of good tumor treatment results. It provides iron / copper-porphyrin nanoparticles with strong catalytic effect and bimetallic ions. These nanoparticles have a suitable particle size, good dispersibility, and stable performance, which can improve the therapeutic effects of PDT and CDT.

[0005] The present invention also provides a method for preparing the above-mentioned iron / copper-porphyrin nanoparticles, which is simple to operate and highly controllable.

[0006] The present invention further provides the application of the above-mentioned iron / copper-porphyrin nanoparticles in the fields of drug delivery and catalysis.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0008] This invention provides a method for preparing iron / copper-porphyrin nanoparticles, comprising the following steps:

[0009] (1) After mixing the iron source, copper source, tetra(4-carboxyphenyl)porphyrin and benzoic acid, add solvent and stir to obtain a mixed solution;

[0010] (2) The resulting mixed solution was heated and reacted. After the reaction was completed, the solution was centrifuged and washed. The resulting brown solid was iron / copper-porphyrin nanoparticles.

[0011] Furthermore, in step (1), the iron source is ferric chloride; the copper source is copper chloride.

[0012] Furthermore, in step (1), the ratio of the amount of iron source, copper source, tetra(4-carboxyphenyl)porphyrin, and benzoic acid added is 0.06g:0.01g:0.008mg:0.6g ~ 0.08g:0.02g:0.009mg:0.8g.

[0013] Furthermore, in step (1), the solvent is N,N-dimethylformamide; the volume of N,N-dimethylformamide solution added to each 0.008-0.009 mg of tetra(4-carboxyphenyl)porphyrin is 15-25 mL.

[0014] Furthermore, in step (1), the stirring is performed at a speed of 800 to 1000 rpm for 10 to 30 minutes.

[0015] Furthermore, in step (2), the heating reaction is at 150°C. o C~180 o React at temperature C for 12-24 h.

[0016] The present invention also provides iron / copper-porphyrin nanoparticles prepared by the above preparation method.

[0017] The iron / copper-porphyrin nanoparticles prepared by this invention have a particle size of 80-200 nm and a specific surface area of ​​180-250 m². 2 g −1 The pore size is 5 ~ 10 nm;

[0018] Another object of the present invention is to provide the application of the above-mentioned iron / copper-porphyrin nanoparticles as a carrier for loading the chemotherapeutic drug doxorubicin.

[0019] Furthermore, the iron / copper-porphyrin nanoparticles are used as drugs in tumor chemokinetics.

[0020] The iron / copper-porphyrin nanoparticles provided by this invention contain a large amount of iron ions, copper ions, and porphyrin. The iron and copper ions can be reduced by glutathione, leading to the Fenton reaction and Fenton-like reactions, thereby generating a large number of hydroxyl radicals and achieving efficient CDT (tumor-induced tumor suppression). The porphyrin can convert oxygen into singlet oxygen under a 660 nm laser, thus achieving efficient PDT (tumor-induced tumor suppression). Its microstructure is an iron / copper-porphyrin nanoscale metal-organic framework, which is stable in a neutral environment. The structure of the iron / copper-porphyrin nanoparticles is degraded by acidic environments and glutathione, releasing iron ions, copper ions, and porphyrin. This allows for more efficient release of these substances in the tumor microenvironment, resulting in better tumor-suppressive effects.

[0021] This invention also provides the potential application of the iron / copper-porphyrin nanoparticles in PDT / CDT combined therapy. The iron / copper-porphyrin nanoparticles prepared by this invention have a large specific surface area, good stability, uniform particle size, good biocompatibility, and excellent in vitro and in vivo antitumor effects, achieving good PDT / CDT combined therapy results.

[0022] Compared with the prior art, the present invention has the following significant advantages:

[0023] (1) The iron / copper-porphyrin nanoparticles prepared by the present invention have the characteristics of uniform particle size and good stability; at the same time, the preparation method is simple and the conditions are easy to control, and no inducing agent or catalyst is required.

[0024] (2) In the application of tumor treatment, the iron and copper ions released by the iron / copper-porphyrin nanoparticles can better consume glutathione, promote the accumulation of hydroxyl radicals and singlet oxygen, and achieve the purpose of improving the tumor treatment effect. Attached Figure Description

[0025] Figure 1 This is a TEM image of the iron / copper-porphyrin nanoparticles prepared in Example 1 of this invention;

[0026] Figure 2 The image shows the ultraviolet absorption spectrum of the iron / copper-porphyrin nanoparticles prepared in Example 1 of this invention.

[0027] Figure 3 Nitrogen adsorption-desorption curves of iron / copper-porphyrin nanoparticles;

[0028] Figure 4 Pore ​​size diagram of iron / copper-porphyrin nanoparticles;

[0029] Figure 5 To assess the stability of iron / copper-porphyrin nanoparticles under different conditions;

[0030] Figure 6The iron and copper ion release curves of iron / copper-porphyrin nanoparticles in different pH buffer solutions are shown.

[0031] Figure 7 The iron and copper ion release curves of iron / copper-porphyrin nanoparticles at different glutathione concentrations are shown.

[0032] Figure 8 Line graph showing the •OH generation after co-incubation of iron / copper-porphyrin nanoparticles with H2O2 at different concentrations, as detected by MB.

[0033] Figure 9 To detect the effects of different concentrations of iron / copper-porphyrin nanoparticles co-incubated with O2 in ABDA 1 Line graph showing O2 generation;

[0034] Figure 10 To detect the production of intracellular reactive oxygen species in MCF-7 cells after co-incubation with iron / copper-porphyrin nanoparticles by flow cytometry;

[0035] Figure 11 The intracellular glutathione content of MCF-7 cells after co-incubation with iron / copper-porphyrin nanoparticles was determined using a glutathione assay kit.

[0036] Figure 12 Figure showing the cytotoxicity assay results of different concentrations of iron / copper-porphyrin nanoparticles on MCF-7 cells;

[0037] Figure 13 The figure shows the results of measuring the activity of different concentrations of iron / copper-porphyrin nanoparticles on MCF-7 cells. Detailed Implementation

[0038] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0039] As described in the background section, porphyrin-based nMOFs with a single metal ion do not effectively consume glutathione in the tumor microenvironment, thus resulting in poor therapeutic efficacy.

[0040] Therefore, the purpose of this invention is to provide iron / copper-porphyrin nanoparticles, their preparation method, and applications. This invention uses ferric chloride, copper chloride, tetrakis(4-carboxyphenyl)porphyrin, and benzoic acid as raw materials to prepare iron / copper-porphyrin nanoparticles via a solvothermal reaction in N,N-dimethylformamide. This synthesis method is simple and highly operable; the obtained product has uniform particle size and good stability. Furthermore, these iron / copper-porphyrin nanoparticles exhibit excellent peroxidase activity and can be used for PDT / CDT combined therapy, including for tumors.

[0041] To enable those skilled in the art to better understand the technical solution of this application, the technical solution of this application will be described in detail below with reference to specific embodiments.

[0042] The test materials used in the embodiments of this invention are all conventional test materials in the art and can be purchased through commercial channels.

[0043] Example 1

[0044] Preparation and characterization of iron / copper-porphyrin nanoparticles

[0045] The preparation method of iron / copper-porphyrin nanoparticles is as follows: 0.06 g of ferric chloride, 0.01 g of copper chloride, 0.008 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.6 g of solid benzoic acid were added to round-bottom flasks respectively. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixed solution was then heated to 160°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron / copper-porphyrin nanoparticles.

[0046] An appropriate amount of iron / copper-porphyrin nanoparticles was added to anhydrous ethanol to prepare a 0.5 mg / mL solution. The sample was then dropped onto a copper grid to prepare a transmission electron microscopy (TEM) sample. The sample was observed using a TEM. Figure 1 TEM images of the iron / copper-porphyrin nanoparticles show that the particles are relatively uniformly distributed, with individual particles having a diameter of approximately 93 nm.

[0047] An appropriate amount of iron / copper-porphyrin nanoparticles was added to N,N-dimethylformamide solution to prepare a 1 mg / mL solution. An appropriate amount of porphyrin was added to N,N-dimethylformamide solution to prepare a 0.01 mg / mL solution. The absorption curves of the iron / copper-porphyrin nanoparticles and porphyrin were detected using a UV spectrophotometer. Figure 2 The ultraviolet absorption spectrum of iron / copper-porphyrin nanoparticles shows that the ultraviolet absorption peak of iron / copper-porphyrin nanoparticles does not change significantly compared with the ultraviolet absorption peak of porphyrin, indicating that the optical properties of porphyrin in iron / copper-porphyrin nanoparticles have not changed.

[0048] Take an appropriate amount of iron / copper-porphyrin nanoparticle solution, centrifuge at 10000 rpm for 10 min to collect the precipitate, and dry it in a vacuum drying oven for BET determination. Figure 3 Nitrogen adsorption-desorption curves of iron / copper-porphyrin nanoparticles and Figure 4The pore size curves of the iron / copper-porphyrin nanoparticles show that their specific surface area is 180~250 m² / g. 2 g −1 The pore size is 5 ~ 10 nm;

[0049] An appropriate amount of iron / copper-porphyrin nanoparticles was added to different media to prepare solutions with a concentration of 1 mg / mL. These solutions were then incubated at room temperature for 7 days, and the particle size change was measured using DLS. Figure 5 The stability curves of iron / copper-porphyrin nanoparticles under different conditions show that the particle size of iron / copper-porphyrin nanoparticles does not change significantly after being placed in different media for 7 days.

[0050] Example 2

[0051] Determination of the degradation properties of iron / copper-porphyrin nanoparticles

[0052] In this embodiment, the degradation performance of iron / copper-porphyrin nanoparticles in a simulated tumor microenvironment is mainly investigated. The specific experimental steps are as follows:

[0053] 0.06 g of ferric chloride, 0.01 g of copper chloride, 0.008 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.6 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixed solution was then heated to 160°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron / copper-porphyrin nanoparticles.

[0054] The prepared iron / copper-porphyrin nanoparticle solutions were added to 2 mL of phosphate buffer at pH 7.4 and pH 6.5, respectively, and placed in 10000 kDa dialysis bags. Dialysis was performed in 20 mL of phosphate buffer at pH 7.4 and pH 6.5. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to detect the release levels of copper and iron ions in the dialysate at different time points. Figure 6 The results show that iron and copper ions are released to a certain extent in phosphate buffer at pH 6.5, indicating that iron / copper-porphyrin nanoparticles have a certain acid-responsive degradation ability.

[0055] The prepared iron / copper-porphyrin nanoparticle solutions were added to 2 mL of acidic phosphate buffer (pH 6.5) containing different concentrations of glutathione (0, 2, 5, 10, 12 mM), respectively. These solutions were then placed in 10000 kDa dialysis bags and dialyzed for 6 h in 20 mL of acidic phosphate buffer containing different concentrations of glutathione. Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to detect the release levels of copper and iron ions in the dialysate at different time points. Figure 7 The iron / copper-porphyrin nanoparticles showed the best release and consumption of iron and copper ions in acidic phosphate buffer containing 5 mM glutathione, indicating that the iron / copper-porphyrin nanoparticles have good glutathione-responsive degradation ability.

[0056] Example 3

[0057] Determining the performance of iron / copper-porphyrin nanoparticles in generating hydroxyl radicals and singlet oxygen

[0058] In this embodiment, the performance of iron / copper-porphyrin nanoparticles in generating hydroxyl radicals and singlet oxygen in a simulated tumor microenvironment is mainly investigated. The specific experimental steps are as follows:

[0059] 0.06 g of ferric chloride, 0.01 g of copper chloride, 0.008 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.6 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixed solution was then heated to 160°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron / copper-porphyrin nanoparticles.

[0060] The ability of iron and copper ions in the prepared iron / copper-porphyrin nanoparticles to undergo Fenton and Fenton-like reactions was detected using methylene blue (MB). Iron / copper-porphyrin nanoparticles, MB, and hydrogen peroxide were mixed in a 5 mM acidic phosphate buffer to prepare solutions with final concentrations of 0, 50, 100, and 200 μg / mL for iron / copper-porphyrin nanoparticles, 10 μM for MB, and 100 μM for hydrogen peroxide. After 0.5 h, the absorption spectrum of MB was measured using a UV spectrophotometer. Figure 8 As shown, the absorption peak of MB gradually decreases with increasing concentration of iron / copper-porphyrin nanoparticles, indicating that iron / copper-porphyrin nanoparticles can catalyze hydrogen peroxide to •OH, and that the ability of iron and copper ions to undergo Fenton and Fenton-like reactions gradually increases with increasing concentration.

[0061] The iron / copper-porphyrin nanoparticles prepared above were tested using 9,10-anthratrium-di(methylene)dimalonic acid (ABDA) to catalyze the conversion of O2 to... 1 O2 capacity. Iron / copper-porphyrin nanoparticles and ABDA were mixed in an acidic phosphate buffer containing 5 mM to prepare solutions with final concentrations of 0, 50, 100, and 200 μg / mL for the iron / copper-porphyrin nanoparticles and a final concentration of 20 μM for the ABDA. The solutions were irradiated with a 660 nm laser for 10 min, and the absorption spectrum of ABDA was measured using a UV spectrophotometer after 0.5 h. Figure 9As shown, the absorption peak of ABDA gradually weakens with increasing concentration of iron / copper-porphyrin nanoparticles, indicating that iron / copper-porphyrin nanoparticles can convert O2 into... 1 O2 has a conversion ability that gradually weakens with increasing concentration.

[0062] Example 4

[0063] Determining the doxorubicin loading effect of iron / copper-porphyrin nanoparticles

[0064] In this embodiment, the loading efficiency of iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles for doxorubicin was mainly determined. The specific experimental steps are as follows:

[0065] 0.06 g of ferric chloride, 0.01 g of copper chloride, 0.008 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.6 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixed solution was then heated to 160°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron / copper-porphyrin nanoparticles.

[0066] 0.05 g of ferric chloride, 0.006 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.56 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixture was then heated to 145°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron-porphyrin nanoparticles.

[0067] The loading efficiency of iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles was determined using a UV spectrophotometer. Different amounts of doxorubicin (0, 0.5, 1, 1.5, and 2 mg) were added to 5 mL of iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles, respectively. The mixtures were stirred at room temperature for 12 h. After the reaction, the loaded iron / copper-porphyrin nanoparticles or iron-porphyrin nanoparticles were obtained by centrifugation. The doxorubicin content in the supernatant after centrifugation was measured, and the loading efficiency of doxorubicin was determined by calculating the ratio of the doxorubicin content in the supernatant to the amount of doxorubicin added. Figure 10 As shown, with the continuous increase of doxorubicin dosage, the loading efficiency of iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles for doxorubicin gradually decreased. When the dosage of doxorubicin reached 2 mg, the loading efficiency no longer changed, indicating that the drug loading had reached saturation. In addition, the incorporation of copper ions did not significantly affect the drug loading capacity of iron / copper-porphyrin nanoparticles.

[0068] Example 5

[0069] Determining the levels of reactive oxygen species and glutathione, as well as the cell-killing effect, of iron / copper-porphyrin nanoparticles in tumor cells.

[0070] In this embodiment, we mainly explore the ability of iron / copper-porphyrin nanoparticles to generate reactive oxygen species and their cell-killing effect in tumor cells. The specific experimental steps are as follows:

[0071] 0.06 g of ferric chloride, 0.01 g of copper chloride, 0.008 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.6 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixed solution was then heated to 160°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron / copper-porphyrin nanoparticles.

[0072] 0.05 g of ferric chloride, 0.006 mg of tetrakis(4-carboxyphenyl)porphyrin, and 0.56 g of solid benzoic acid were added separately to round-bottom flasks. 20 mL of N,N-dimethylformamide was added, and the mixture was stirred at 900 rpm for 20 min. The resulting mixture was then heated to 145°C in an oil bath. o C, react for 12 h, centrifuge and wash after the reaction, the brown solid obtained is iron-porphyrin nanoparticles.

[0073] Flow cytometry was used to detect the production of reactive oxygen species (•OH +) in MCF-7 tumor cells by the iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles prepared above. 1 O2 content. Different concentrations (0, 10, 40, 60, 80, 100 μg / mL) of iron / copper-porphyrin nanoparticles or iron-porphyrin nanoparticles were co-incubated with MCF-7 cells for 2 h. After incubation, the cells were irradiated with a 660 nm laser for 10 min, followed by a further 2 h of incubation. The level of intracellular reactive oxygen species was detected using the DCFH-DA probe. Figure 11 As shown, the fluorescence intensity gradually increases with increasing particle concentration, indicating that iron / copper-porphyrin nanoparticles can promote the increase of intracellular reactive oxygen species in tumor cells in a concentration-dependent manner. In contrast, iron-porphyrin nanoparticles have a lower ability to increase intracellular reactive oxygen species content than iron / copper-porphyrin nanoparticles.

[0074] The glutathione content in MCF-7 tumor cells was detected using flow cytometry with the iron / copper-porphyrin nanoparticles and iron-porphyrin nanoparticles prepared above. Different concentrations (0, 10, 40, 60, 80, 100 μg / mL) of iron / copper-porphyrin nanoparticles or iron-porphyrin nanoparticles were co-incubated with MCF-7 cells for 2 h, followed by irradiation with a 660 nm laser for 10 min, and then further incubated for 2 h. Intracellular glutathione levels were detected using a glutathione assay kit. Figure 12 As shown, glutathione gradually decreases with increasing particle concentration, indicating that iron / copper-porphyrin nanoparticles can promote the reduction of intracellular glutathione in tumor cells in a concentration-dependent manner. In contrast, iron-porphyrin nanoparticles have a lower capacity to deplete intracellular glutathione than iron / copper-porphyrin nanoparticles.

[0075] The effect of iron / copper-porphyrin nanoparticles or iron-porphyrin nanoparticles on the viability of MCF-7 cells was detected using the MTT assay. 1×10⁻⁶ nanoparticles were added to each well of a 96-well plate. 4 MCF-7 cells were cultured in a constant-temperature cell culture incubator for 24 h. Then, different concentrations (0, 10, 40, 60, 80, 100 μg / mL) of iron / copper-porphyrin nanoparticles or iron-porphyrin nanoparticles were co-incubated with MCF-7 cells for 2 h, followed by irradiation with a 660 nm laser for 10 min, and then further incubated for 22 h. Afterward, the culture medium was aspirated, and medium containing MTT was added. The cells were cultured for 3 h, the culture medium was discarded, and 150 μL of DMSO was added to each well. The cells were incubated for 10 min, and the absorbance values ​​at each concentration were read using a microplate reader to calculate the viability. Figure 13 As shown, the survival rate of MCF-7 cells gradually decreased with increasing particle concentration, indicating that iron / copper-porphyrin nanoparticles have a concentration-dependent cytotoxic effect on tumor cells. In contrast, iron-porphyrin nanoparticles showed lower tumor cell killing ability than iron / copper-porphyrin nanoparticles.

[0076] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. Use of iron / copper-porphyrin nanoparticles as a carrier for loading chemotherapeutic drug doxorubicin, characterized in that, The preparation method of the iron / copper-porphyrin nanoparticles comprises the following steps: (1) mixing an iron source, a copper source, tetra(4-carboxyphenyl) porphyrin and benzoic acid, then adding a solvent to stir to obtain a mixed solution; (2) heating the obtained mixed solution to react, centrifuging and washing after the reaction is completed, and obtaining a brown solid as the iron / copper-porphyrin nanoparticles; In step (1), the iron source is ferric chloride; and the copper source is cupric chloride. In step (1), the adding amount ratio of the iron source, the copper source, tetra(4-carboxyphenyl) porphyrin and benzoic acid is 0.06-0.08 g:0.01-0.02 g:0.008-0.009 mg:0.6-0.8 g.

2. Use according to claim 1, characterized in that, In step (1), the solvent is N,N-dimethylformamide; and the volume of the N,N-dimethylformamide solution added in each 0.008-0.009 mg of tetra(4-carboxyphenyl) porphyrin is 15-25 mL.

3. Use according to claim 1, characterized in that, In step (1), the stirring is performed at a speed of 800-1000 rpm for 10-30 min.

4. Use according to claim 1, characterized in that, In step (2), the heating reaction is at 150 o C~180 o C at a temperature of 12 ~ 24 h.

5. Use according to any one of claims 1 to 4, characterized in that, The iron / copper-porphyrin nanoparticle has a particle size of 80 ~ 200 nm, a specific surface area of 180 ~ 250 m 2 g −1 , and a pore size of 5 ~ 10 nm.

6. Use according to claim 1, characterized in that, The iron / copper-porphyrin nanoparticles are applied as a drug in tumor chemical kinetics treatment.

Citation Information

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