CN110876804B - Preparation and application of porous mangano-manganic oxide nano probe - Google Patents

Preparation and application of porous mangano-manganic oxide nano probe Download PDF

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CN110876804B
CN110876804B CN201911067190.8A CN201911067190A CN110876804B CN 110876804 B CN110876804 B CN 110876804B CN 201911067190 A CN201911067190 A CN 201911067190A CN 110876804 B CN110876804 B CN 110876804B
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刘笔锋
曾雪梅
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Huazhong University of Science and Technology
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Abstract

The invention belongs to the technical field of nano biological materials, and particularly relates to preparation and application of a porous manganous-manganic oxide nano probe. The invention carries out high-temperature calcination on the manganese metal organic framework nano material Mn-MOF prepared by a one-pot method to obtain the porous trimanganese tetroxide nano material. Thereby Mn is present3O4When the carrier is used for cancer treatment, the surrounding hydrogen peroxide can be catalyzed into oxygen, so that the oxygen content in tumor cells is improved, and the photodynamic efficiency is further increased; meanwhile, Mn3O4The cell-free cancer-treating agent also has the capacity of GSH consumption, and can consume GSH in cells to prevent the GSH from removing free radicals in photodynamic reaction when cancer treatment is carried out, so that the photodynamic efficiency is greatly increased; and after a series of modification of the upper nuclear targeting sequence, the nano material is endowed with the property of nuclear entry, so that the nuclear entry photodynamic therapy with enhanced treatment efficiency is realized, and the tumor cells are effectively killed.

Description

Preparation and application of porous mangano-manganic oxide nano probe
Technical Field
The invention belongs to the technical field of nano biological materials, and particularly relates to preparation and application of a porous manganous-manganic oxide nano probe.
Background
Compared with the traditional tumor treatment methods such as surgery, radiotherapy, chemotherapy and the like, the photodynamic therapy is a very popular tumor treatment method due to the advantages of high selectivity, small damage to normal tissues, low toxicity, repeated treatment and the like.
The photodynamic is mainly composed of three factors: photosensitive molecules, oxygen and a laser light source with a specific wave number. The effect of photodynamic therapy depends on the efficiency of photodynamic therapy, and high-efficiency photoreaction can generate a large amount of active oxygen, thereby realizing good photodynamic therapy. Various factors affect the photodynamic effect, such as the power of the laser source, the content of ambient oxygen, the concentration of photosensitive molecules, and the lifetime of active oxygen.
The current research on photodynamic therapy is mostly based on increasing the oxygen content around cells or in tumors, which can actually greatly improve the efficiency, but the intracellular reaction is a steady-state equilibrium reaction, and the free radicals generated by the photoreaction have a very short life span, and a kind of free radical scavenger such as GSH exists in the cells in a very short time to scavenge the free radicals so as to protect the cells, so that the problem of increasing the oxygen content to improve the efficiency and preventing the free radicals generated with high efficiency from being scavenged by the GSH is urgent.
Disclosure of Invention
Aiming at the defects or the improvement requirements of the prior art, the invention provides preparation and application of a porous trimanganese tetroxide nano probe, which is characterized in that a nano material Mn-MOF of a manganese metal organic framework prepared by a one-pot method is calcined at high temperature to obtain a porous trimanganese tetroxide nano material, and the porous trimanganese tetroxide nano material is used for preparing a nuclear photodynamic tumor treatment probe, so that the technical problems that free radicals generated by photoreaction of the photodynamic tumor treatment probe in the prior art are short in service life and are easy to be removed by GSH to cause poor photodynamic treatment effect are solved.
In order to achieve the above objects, according to one aspect of the present invention, there is provided a method for preparing a porous manganomanganic oxide nano material, comprising the steps of:
(1) synthesizing a manganese metal organic framework nano material Mn-MOF by a one-pot method;
(2) and (2) calcining the manganese metal organic framework nano material Mn-MOF obtained in the step (1) to obtain the porous trimanganese tetroxide nano material.
Preferably, step (1) is specifically: manganese ions of manganese chloride tetrahydrate are used as metal ions, 2-methylimidazole is used as an organic framework, and a nano material Mn-MOF of the metal organic framework is synthesized by a one-pot method.
Preferably, the molar ratio of the manganese chloride tetrahydrate to the 2-methylimidazole is 1: 12-85.
Preferably, the step (2) is specifically: the calcination is carried out within the range of 300-500 ℃ for 3-5 hours.
According to another aspect of the invention, the porous mangano-manganic oxide nano material obtained by the preparation method is provided.
According to another aspect of the invention, the application of the porous mangano-manganic oxide nano material is provided, which is used for preparing a nano probe for treating tumors.
Preferably, the nano probe for treating tumor is a nano probe for treating tumor by nuclear photodynamic.
Preferably, the porous mangano-manganic oxide nano material is also modified with polyethylene glycol.
Preferably, the porous manganomanganic oxide nano material is also loaded with photosensitive molecules.
Preferably, the porous mangano-manganic oxide nano material is also modified with a core-entering sequence SH-NLS containing sulfydryl.
Preferably, before application, the porous manganous-manganic oxide nano material is subjected to modification of polyethylene glycol, loading of photosensitive molecules and modification of nuclear sequences in sequence.
In general, compared with the prior art, the above technical solution contemplated by the present invention can achieve the following beneficial effects:
(1) the invention carries out high-temperature calcination on the manganese metal organic framework nano material Mn-MOF prepared by a one-pot method to obtain the porous trimanganese tetroxide nano material. The nano material has a regular cube shape, the longest cube side length is 40-50 nanometers, and the nano material has a porous structure.
(2) The invention synthesizes organic metal frame nanometer material of precursor manganese by a one-pot method, removes the organic frame which is not high temperature resistant by high temperature calcination, and obtains manganese oxide Mn3O4. On the basis, the water-soluble polyethylene glycol is modified, so that the material is better in water solubility and biocompatibility.
(3) The invention preferably uses MOF as precursor, and makes good use of the permanent porous structure of the MOF.
(4) Mn according to the invention3O4Inherently having peroxidase catalytic activity, thereby Mn3O4When the carrier is used for cancer treatment, the surrounding hydrogen peroxide can be catalyzed into oxygen, so that the oxygen content in tumor cells is improved, and the photodynamic efficiency is further increased; meanwhile, Mn3O4The cell-free cancer-treating agent also has the capacity of GSH consumption, and can consume GSH in cells to prevent the GSH from removing free radicals in photodynamic reaction when cancer treatment is carried out, so that the photodynamic efficiency is greatly increased; and after a series of modification of the upper nuclear targeting sequence, the nano material is endowed with the property of nuclear entry, so that the nuclear entry photodynamic therapy with enhanced treatment efficiency is realized, and the tumor cells are effectively killed.
(5) Mn synthesized by the invention3O4The nanoprobe can be well applied to a mouse xenograft model, and well inhibits the growth of mouse tumors through enhanced nuclear entry photodynamic therapy.
Drawings
FIG. 1 is a diagram of synthetic Mn-MOF and Mn3O4Transmission electron microscopy, scale bars is 100 nm.
FIG. 2 shows synthesized Mn3O4-PEG/C&N is used for the characterization of the decomposition of hydrogen peroxide in the catalytic system, the concentration of the probe used in the figure is 50 mug/mL, the concentration of hydrogen peroxide is 100mM, and the amount of dissolved oxygen in the system is mg/L and is detected by a dissolved oxygen meter.
FIG. 3 shows synthesized Mn3O4-PEF/C&The effect of N on GSH depletion, as seen by the probe concentrationThe GSH in the system gradually becomes less as the degree increases.
FIG. 4 shows the distribution of probes in the cells of mouse breast cancer cells 24h after 50. mu.g/mL of the probes are incubated.
FIG. 5 shows Mn3O4-PEG/C&N was used as a result of tumor growth inhibition in a mouse xenografted tumor model.
FIG. 6 is Mn3O4-PEG/C&N is used in tumor entity map obtained after tumor growth inhibition treatment in a tumor model of mouse xenograft.
FIG. 7 is a composite MOF material (FIG. 7a) and Mn3O4As a result of BET characterization of the material (fig. 7b), it can be seen that Mn3O4 has a larger specific surface area.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The invention provides a preparation method of a porous manganous-manganic oxide nano material, which comprises the following steps:
(1) synthesizing a manganese metal organic framework nano material Mn-MOF by a one-pot method;
(2) and (2) calcining the manganese metal organic framework nano material Mn-MOF obtained in the step (1) to obtain the porous trimanganese tetroxide nano material.
In some embodiments, step (1) is specifically: with manganese chloride tetrahydrate (MnCl)2·4H20) The manganese ion is metal salt, 2-Methylimidazole (2-Methylimidazole,2-mIm) is used as an organic framework, and the nano material Mn-MOF of the metal organic framework is synthesized by a one-pot method.
The one-pot method is to mix and stir an aqueous solution of manganese chloride tetrahydrate and an aqueous solution of an organic framework to prepare Mn-MOF. In some embodiments, the amount of manganese chloride tetrahydrate and organic framework can be adjusted as desired to obtain Mn-MOFs with suitable morphology and loading density. The molar ratio of the manganese chloride tetrahydrate to the 2-methylimidazole is preferably 1: 12-85. In a reaction system, the using amount of manganese chloride tetrahydrate is 1-3mmol of substances, and the using amount of organic framework 2-methylimidazole is 3-7g by mass.
In some embodiments, step (2) is specifically: the calcination is carried out within the range of 300-500 ℃ for 3-5 hours. The calcination of the invention is carried out in an air atmosphere.
The invention also provides the porous trimanganese tetroxide nano material obtained by the preparation method.
The preparation method comprises the following steps that (1) the manganese metal organic framework nano material Mn-MOF prepared in the step comprises a stacked cube structure, and the longest side length of the Mn-MOF is 40-50 nm; the porous manganomanganic oxide obtained after calcination keeps the structure of the cube stack, but obviously the pore structure is greatly increased.
The porous mangano-manganic oxide nano probe prepared by the invention has the catalytic activity of peroxidase, can catalyze hydrogen peroxide into oxygen, and preferably can catalyze the hydrogen peroxide enriched in cancer cells to be converted into oxygen and simultaneously can enhance the efficiency of photodynamic therapy when the probe is applied to cell therapy or biotherapy.
The porous mangano-manganic oxide nano probe prepared by the invention has GSH consumption capability, and preferably, when the probe is applied to cell therapy or living body therapy, the GSH in cells or cancer can be consumed, and generated active oxygen is prevented from being eliminated by the GSH.
The precursor of the porous manganous manganic oxide nano probe provided by the invention is metal organic framework Mn-MOF, and Mn is obtained by high-temperature calcination3O4Compared with Mn-MOF, the catalyst has larger specific surface area and porous structure, has better catalytic performance, and is more convenient to load photosensitive molecules such as Ce 6.
The application of the porous mangano-manganic oxide nano material can be used for preparing a nano probe for treating tumors.
In some embodiments, the tumor-treating nanoprobe is an enhanced endonuclear photodynamic tumor-treating nanoprobe.
In some embodiments, the porous trimanganese tetroxide nanomaterial is polyethylene glycol modified prior to application. The maleimide-containing compound, preferably Mn, may be ligatively modified, for example by reaction with MPTMS and TCEP3O4The probe can be connected with polyethylene glycol (MAL-PEG) modified with maleimide to improve the water solubility and biocompatibility of the probe as a nano probe.
In some embodiments, the porous manganomanganic oxide nanomaterial is loaded with photosensitive molecules before application. The permanent porous structure can realize the loading of a plurality of small molecules through physical adsorption and hollow porous loading, preferably the small molecules are photosensitive molecules, and preferably the photosensitive molecules are Ce 6. In some embodiments, the trimanganese tetroxide nanomaterial Mn modified by polyethylene glycol is3O4PEG photosensitive molecules capable of being loaded in Mn with a porous structure by stirring with the photosensitive molecules in aqueous solution3O4In the pores of (A), the resulting probe is represented by Mn3O4-PEG/C。
In some embodiments, the porous manganomanganic oxide nanomaterial is modified by a thiol-containing core sequence SH-NLS before application. Specifically, by adding Mn3O4The PEG/C is reacted with a core-entering sequence HS-NLS modified with sulfydryl to obtain the nano probe with core-entering property, and the reaction is realized through a metal-sulfur bond.
In some embodiments, when the porous mangano-manganic oxide nano material prepared by the invention is used for preparing a nano probe for treating tumors, modification of polyethylene glycol, loading of photosensitive molecules and modification of nuclear sequences are sequentially carried out.
The invention discloses a preparation method of a porous manganous-manganic oxide nano probe and application of the porous manganous-manganic oxide nano probe in enhanced nuclear photodynamic therapy, belonging to the technical field of nano biomaterials. The manganic manganous oxide Mn3O4By organic goldThe material belongs to a framework (Metal Organic Frameworks, MOFs) one-pot method preparation, is obtained by high-temperature calcination after preparation, has a permanent porous structure on the surface, and can modify required small molecules through physical loading. Synthesized Mn3O4The peroxidase catalytic performance is good, surrounding hydrogen peroxide can be rapidly catalyzed into oxygen, and simultaneously, GSH can be consumed in the presence of glutathione GSH, and the two properties greatly contribute to the photodynamic efficiency if applied to photodynamic therapy. It is known that photodynamic is the treatment of tumor by photosensitive molecules under the irradiation of laser with a specific wavelength, and the photosensitive molecules generate photoreaction to generate active oxygen such as singlet oxygen or free radicals, but the efficiency of photodynamic treatment is greatly limited by the quantity and the life span of the generated active oxygen, and in addition, GSH existing in cells or in physiological environment can act as a free radical scavenger, resulting in low photodynamic efficiency. Therefore, how to solve the problem of efficiency of the photodynamic light is not easy. In addition, most of the existing probes based on photodynamic therapy do not have specific targeting, and cannot cause damage to specific subcellular structures. Endows the photodynamic probe with the nuclear entering characteristic, and can greatly improve the effect of photodynamic therapy. The invention synthesizes Mn3O4To solve the above problems, Mn to be synthesized3O4Surface modification of polyethylene glycol to increase Mn3O4Then the photosensitive molecule Chlorin e6(Chlorin e6, Ce6) and the nuclear entering sequence NLS are modified, and Mn is synthesized3O4-PEG/C&N has good effect in photodynamic therapy due to Mn3O4The hydrogen peroxide catalytic ability and GSH consumption ability, and the inclusion of NLS, have resulted in more efficient photodynamic therapy. The probe has good photodynamic effect on the cellular level and the living body level.
The invention provides a method for synthesizing a porous manganomanganic oxide nano material taking an organic metal framework as a precursor, and the porous manganomanganic oxide nano material is applied to enhanced photodynamic therapy of tumors. Mn calcined at high temperature with MOF as precursor3O4The porous structure with very large specific surface area facilitates subsequent modification and loading of small molecules. While Mn3O4Inherently possess the catalytic activity of peroxidases and the ability to consume GSH, and thus, enhanced photodynamic therapy can be achieved by increasing the oxygen content while sparing the active oxygen from being scavenged.
In some embodiments, the synthesis of the porous trimanganese tetroxide nanoprobe provided by the invention comprises the steps of firstly synthesizing a precursor thereof, specifically, synthesizing manganese chloride tetrahydrate and 2-mIm by a one-pot method to obtain an organic metal frame of manganese, and calcining at high temperature to obtain manganese oxide Mn3O4. Then, after reaction with MPTMS and TCEP, polyethylene glycol with maleimide group is modified to improve the water solubility and biocompatibility of the probe, and then photosensitive molecules and nuclear sequences are modified to carry out subsequent enhanced photodynamic therapy, so that the probe can have a very good tumor inhibition effect when applied to living bodies.
The present invention further provides the above Mn3O4The preparation method of the probe comprises the following steps:
(1) manganese ions of manganese chloride tetrahydrate are used as metal ions, 2-methylimidazole is used as an organic framework, and Mn-MOF is synthesized through a one-pot method.
(2) Calcining the Mn-MOF in the step (1) at high temperature to obtain Mn3O4。
(3) Mn in (2)3O4After reaction with MPTMS and TCEP, modifying polyethylene glycol with maleimide to obtain Mn3O4-PEG。
(4) And (3) loading a photosensitive molecule Ce6 and an entry sequence NLS.
Specifically, in the step (1), the metal-organic framework of manganese is prepared by the following method:
1) respectively preparing solutions of manganese chloride tetrahydrate and 2-methylimidazole for later use: specifically, 1-3mmol of manganese chloride tetrahydrate in 3mL of water and 3-7g of 2-methylimidazole in 20mL of water are dissolved for later use.
2) Dropwise adding a tetrahydrate manganese chloride solution into the imidazole solution prepared in the step 1) under vigorous stirring, continuously stirring at room temperature for 5-7h to finally change the color from colorless to dark brown, and centrifugally washing away unreacted manganese ions and imidazole to obtain dark brown precipitate, namely the manganese organic metal framework.
In the step (2), the obtained Mn-MOF is calcined in a muffle furnace at high temperature of 300-500 ℃ for 3-5 h.
Some examples in step (3), Mn prepared in (2)3O4Dissolving in ethanol solution, adding MPTMS under continuous and uniform stirring, reacting at room temperature in dark place, centrifuging, washing off unreacted MPTMS molecules with ultrapure water to obtain Mn3O4-MPTMS was resuspended in PBS solution, nitrogen gas was blown in under continuous stirring to remove oxygen dissolved in the reaction system, then TCEP was added, 10mg of MAL-PEG was added after reaction, centrifugation was carried out, unreacted PEG was removed by washing with ultrapure water to obtain Mn3O4-PEG. The effect of the modified PEG here is mainly to give the synthesized MOF better water solubility and biocompatibility.
Some examples in step (4), Mn prepared in (3)3O4Reacting PEG with appropriate amount of Ce6 solution and NLS, stirring overnight, centrifuging, washing with ultrapure water three times to remove unreacted Ce6 and NLS to obtain Mn3O4-PEG/C&N。
The invention also provides the application of the material in a mouse tumor model of xenotransplantation.
The following are examples:
example 1
Porous Mn3O4The preparation method of the nanoprobe comprises the following steps:
(1) manganese ions of manganese chloride tetrahydrate are used as metal ions, 2-methylimidazole is used as an organic framework, and Mn-MOF is synthesized through a one-pot method.
(2) Calcining the Mn-MOF in the step (1) at high temperature to obtain Mn3O4。
(3) Mn in (2)3O4After reaction with MPTMS and TCEP, modifying polyethylene glycol with maleimide to obtain Mn3O4-PEG。
(4) And (3) loading a photosensitive molecule Ce6 and an entry sequence NLS.
Specifically, in the step (1), the metal-organic framework of manganese is prepared by the following method:
1) respectively preparing solutions of manganese chloride tetrahydrate and 2-methylimidazole for later use: dissolving 1.55mmol of manganese chloride tetrahydrate in 3mL of ultrapure water, and uniformly dispersing by ultrasonic to obtain an aqueous solution of cerium nitrate hexahydrate; 5.5g of 2-methylimidazole is dissolved in 20mL of water and uniformly dispersed by ultrasonic to obtain an aqueous solution of imidazole for later use.
2) Adding 3mL of manganese chloride tetrahydrate solution into 20mL of 1) under vigorous stirring, continuously stirring at room temperature for 6h until the color is changed from colorless to dark brown, and centrifuging to remove unreacted manganese ions and imidazole to obtain dark brown precipitate, namely the organic metal framework of manganese.
In the step (2), the obtained Mn-MOF is calcined in a muffle furnace at a high temperature of 300 ℃ for 5 h.
In the step (3), Mn prepared in the step (2)3O4Weighing 10mg, dissolving in 20mL ethanol solution, adding 800 μ L of 4% MPTMS under continuous uniform stirring, reacting at room temperature in a dark place for 2h, centrifuging at 6000rpm for 10min, washing with ultrapure water for three times to remove unreacted MPTMS molecules to obtain Mn3O4-MPTMS was resuspended in 20mL PBS solution, nitrogen was bubbled through for 30min under continuous stirring to remove dissolved oxygen in the reaction system, then after adding a small scoop of TCEP, 10mg MAL-PEG was added for reaction for 2h, and after centrifugation at 6000rpm for 10min, unreacted PEG was removed by washing three times with ultrapure water to obtain Mn3O4-PEG. The effect of the modified PEG here is mainly to give the synthesized MOF better water solubility and biocompatibility.
In the step (4), Mn prepared in the step (3)3O4Reacting PEG with appropriate amount of Ce6 solution and NLS, stirring overnight, centrifuging at 6000rpm for 10min, washing with ultrapure water three times to remove unreacted Ce6 and NLS to obtain Mn3O4-PEG/C&N。
Example 2
The embodiment provides a method for synthesizing a porous manganous-manganic oxide nano probe, wherein the material is distributed in a cube shape, and the longest side length of the material is 40nm-50 nm;
the material is prepared by the following preparation method:
(1) preparation of MOF
In a vigorously stirred 20mL reaction system containing 5.5g of 2-mIm water, dropwise adding 3mL of a manganese chloride tetrahydrate solution dissolved with 1.55mmol of manganese chloride, continuously stirring at room temperature for 6h to change the color from colorless to dark brown, and centrifuging at 6000rpm for 10min to remove unreacted metal ions and imidazole to obtain dark brown precipitate, namely MOF.
As shown in FIG. 1, the obtained MOF is a transmission electron microscope morphology, and the longest side of the obtained MOF is 50nm and has better dispersibility.
(2)Mn3O4Preparation of
Placing the MOF powder in the step (1) in a muffle furnace for high-temperature calcination at 300 ℃ for 5h to obtain manganese oxide Mn3O4。
As shown in FIG. 1, for the obtained Mn3O4Compared with MOF, the morphology of the transmission electron microscope is not greatly different, but has a more obvious porous structure.
FIG. 7 is a view of the synthesized MOF material (FIG. 7a) and Mn3O4BET characterization of the material (FIG. 7b) it can be seen that the Mn after calcination is comparable to the MOF3O4Has larger specific surface area.
Example 3
The organometallic framework is used for material characterization of enhanced nuclear entry photodynamic, and the steps are as follows:
characterization of the catalytic Properties of the organometallic framework prepared, the Mn to be synthesized3O4-PEG/C&N is dissolved in water, reacts with hydrogen peroxide, and the amount of dissolved oxygen generated by decomposition of hydrogen peroxide in the reaction system is detected within 5 min.
FIG. 2 shows Mn3O4-PEG/C&The result shows that the N can well and continuously catalyze the decomposition of the hydrogen peroxide in a reaction system to generate oxygen.
Characterisation of the Mn produced3O4When GSH capacity is consumed, the GSH is reacted with 1mg/mL GSH for 12h and then measured in a systemContent of GSH.
The results in FIG. 3 show that as the concentration of probe increases, the GSH consumption of the system increases and the GSH concentration decreases.
When the nuclear entering property of the prepared probe is characterized, Mn3O4-PEG/C & N-FITC with the concentration of 50 mu g/mL is added into mouse breast cancer cells for incubation, confocal photographing is carried out after 24h, and the distribution condition of the probe in the cells is observed.
FIG. 4 is the results of the confocal focusing of the cells, showing that the probe is able to perform well into the nucleus, with a large distribution in both the cytoplasm and the nucleus.
Example 4
The porous manganomanganic oxide nano probe is used for enhancing the endonuclear photodynamic therapy to inhibit the growth of the tumor, and the steps are as follows:
(1) preparation of Balb/c mice subcutaneous tumor model: mouse breast cancer cells 4T1 at 37 deg.C with 5% CO2Culturing in DMEM complete medium under the condition, and collecting 5 × 10 when growth state is good6Inoculating the cells into Balb/c mice subcutaneously until the subcutaneous tumor grows to 200mm3Left and right for standby.
(2) Experimental grouping and nanoprobe dose selection: using 500. mu.g/Mn3O4-PEG/C&And (3) carrying out toxicity detection on Balb/c mice by using N, wherein the mice normally move and do not die. The experimental injection of 200. mu.g/body of probe and injection volume of 100. mu.L was selected with reference to the relevant literature and the above results. Mice were then randomly grouped. A probe control group and a light control group are respectively set up.
(3) Combination therapy: tail vein injection of Mn3O4-PEG/C&N, the dosage is 200 mu g/mouse, and the illumination is carried out after 12h (660nm, 160 mW/cm)2，10min)。
(4) The body weight and the tumor volume of the mice are recorded every day, and the tumor volume of the experimental group is found to be greatly inhibited, and other groups have no obvious inhibition phenomenon. The probe can be used for the combined treatment of mouse subcutaneous tumors.
FIG. 5 shows that the synthesized nanoprobe of the invention can well inhibit the growth of mouse tumor by enhanced nuclear entry photodynamic therapy, and other groups have little or poor inhibition effect. Fig. 6 is a pictorial representation of tumors obtained after relevant treatment, in conclusion consistent with fig. 5.
It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.

Claims (7)

1. A preparation method of a porous mangano-manganic oxide nano material is characterized by comprising the following steps:
(1) synthesizing a manganese metal organic framework nano material Mn-MOF by a one-pot method;
(2) calcining the manganese metal organic framework nano material Mn-MOF obtained in the step (1) to obtain a porous manganous manganic oxide nano material, wherein the porous manganous manganic oxide nano material has a regular cube shape, and the longest cube side length is 40-50 nanometers; the step (1) is specifically as follows: taking manganese ions of manganese chloride tetrahydrate as metal ions and 2-methylimidazole as an organic framework, mixing and stirring an aqueous solution of the manganese chloride tetrahydrate and an aqueous solution of the organic framework to prepare a nano material Mn-MOF of the metal organic framework, wherein the molar ratio of the manganese chloride tetrahydrate to the 2-methylimidazole is 1: 12-85; the step (2) is specifically as follows: the calcination is carried out within the range of 300-500 ℃ for 3-5 hours.
2. The porous trimanganese tetroxide nano-material obtained by the preparation method of claim 1.
3. The use of the porous trimanganese tetroxide nanomaterial of claim 2 to prepare a nanoprobe for treating tumors.
4. The use of claim 3, wherein the tumor treating nanoprobe is a nuclear photodynamic tumor treating nanoprobe.
5. The use of claim 3, wherein the porous trimanganese tetroxide nanomaterial is further modified with polyethylene glycol.
6. The use of claim 3, wherein the porous manganomanganic oxide nanomaterial is further loaded with a photosensitive molecule.
7. The use of claim 3, wherein the porous trimanganese tetroxide nanomaterial is further modified with a thiol-containing core sequence SH-NLS.
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