CN108727605B - Hydrogen bond organic framework material constructed based on condensed ring ligand, and preparation method and application thereof - Google Patents
Hydrogen bond organic framework material constructed based on condensed ring ligand, and preparation method and application thereof Download PDFInfo
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Abstract
The invention belongs to the field of porous organic materials, and particularly discloses a hydrogen bond organic framework material constructed based on condensed ring ligands, and a preparation method and application thereof. The material is constructed by taking a condensed ring ligand as an organic framework and utilizing the synergistic action of multiple hydrogen bonds and pi-pi interaction force of the condensed ring ligand; the condensed ring ligand is selected from multi-benzene ring conjugated aromatic hydrocarbon containing carboxyl, and the particle size of the material is 200 nanometers to 50 micrometers. The organic framework material has the characteristics of high specific surface area, permanent pore channels, high chemical and thermal stability, mild synthesis conditions, excellent singlet oxygen generation capacity and the like, and the material has simple preparation method and strong operability, and can freely control the particle size of particles. The material has good biocompatibility and lower biotoxicity, has excellent composite chemical-photodynamic treatment capacity after being further compounded with anticancer drugs, shows excellent cancer treatment effect and has low cancer cell survival rate.
Description
Technical Field
The invention belongs to the field of porous organic materials, and relates to a hydrogen bond organic framework material constructed based on condensed ring ligands, in particular to a hydrogen bond organic framework material constructed based on condensed ring ligands, and a preparation method and application thereof.
Background
Hydrogen bond organic framework materials (HOFs for short) show excellent application prospects in the fields of gas storage/separation, proton conduction and the like due to the characteristics of large specific surface area, good reproducibility and mild synthesis conditions, but the development of the application is limited by the characteristic of low stability.
Cancer causes millions of deaths each year, posing an increasing threat to human health. Chemotherapy is still the most common treatment for cancer today. However, limitations inherent to chemotherapy, including poor side effects, poor pharmacokinetics and poor biodistribution, have forced the search for complex therapies such as chemo-photodynamic and chemo-hyperthermia, which have become effective strategies to break the limitations of single components and eliminate cancer therapy.
Disclosure of Invention
The invention provides a hydrogen bond organic framework material constructed based on condensed ring ligands, which solves the problems of poor stability and incapability of maintaining permanent pore channels of the conventional hydrogen bond organic framework material by utilizing the synergistic action of multiple hydrogen bonds and pi-pi interaction force of the condensed ring ligands, has excellent chemical and thermal stability, and can realize the restoration of crystalline state and specific surface area in an acid environment.
The hydrogen bond organic framework material constructed based on the condensed ring ligand is a hydrogen bond organic framework material constructed by taking the condensed ring ligand as an organic framework and utilizing the synergistic action of multiple hydrogen bonds and pi-pi interaction force of the condensed ring ligand.
According to the present invention, a hydrogen bonding organic framework material comprising a fused ring ligand selected from aromatic compounds comprising a conjugated structure optionally substituted with 1, 2 or more carboxyl groups, such as aromatic compounds comprising a conjugated structure substituted with 1, 2, 3, 4, 5, 6, 7, 8, 9,10 or more carboxyl groups; wherein the aromatic compound including a conjugated structure may include: for example, the aromatic hydrocarbon contains aromatic hydrocarbon formed by conjugation of 2-60 benzene rings; a heteroaromatic compound formed by conjugation of 2 to 60 aromatic heterocycles; or a heteroaromatic compound formed by conjugating at least 1 benzene ring (e.g., 1 to 60) and at least one (e.g., 1 to 60) aromatic heterocycle;
preferably, the number of 1 to 60 means an integer which may be any of 1 to 60, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30; the 2 to 60 means an integer of 2 to 60, for example, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30;
as an example, the aromatic compound having a conjugated structure may be a conjugated aromatic hydrocarbon formed by 2 to 30, for example, 2 to 10 (for example, 2, 3, 4, 5, 6, 7, 8, 9, or 10) benzene rings, and examples thereof may be naphthalene, anthracene, phenalene, pyrene, perylene, and the like;
the aromatic heterocyclic ring may be a 5, 6, 7, 8, 9 or 10 membered aromatic heterocyclic ring containing 1, 2, 3, 4 or 5 heteroatoms selected from nitrogen, oxygen, sulphur;
the conjugation may be achieved by means of fusion or by chemical bond linkage;
according to embodiments of the present invention, the fused ring ligand may be selected from the structures shown below:
for example, the fused ring ligand may be selected from 1, 4-naphthalene dicarboxylic acid, 9, 10-anthracene dicarboxylic acid, 1,3,6, 8-tetrakis (p-carboxyphenyl) pyrene, and the like.
Wherein the particle size of the hydrogen bond organic framework material is 200 nanometers to 50 micrometers; preferably, the particle size is 200 nanometers to 30 micrometers; more preferably, the particle size is from 200 nanometers to 5 micrometers; according to exemplary embodiments of the invention, the particle size may be 200 nanometers, 500 nanometers, 1 micron, 10 microns, 15 microns.
According to the embodiment of the invention, the hydrogen bond organic framework material takes a condensed ring ligand as an organic framework and has a multi-channel structure.
According to an exemplary embodiment of the invention, the hydrogen bonding organic framework material has a specific surface area of between 1000 and 2400 m/g, such as between 2000 and 2200 m/g.
The invention also provides a preparation method of the hydrogen bond organic framework material, which comprises the following steps: and adding a poor solvent into the solution of the condensed ring ligand by adopting a recrystallization method, and fully stirring, standing, centrifuging and cleaning to obtain the hydrogen bond organic framework material constructed based on the condensed ring ligand.
According to the preparation method of the present invention, the solvent in the solution of the fused ring ligand is a solvent in which the fused ring ligand can be dissolved, and is preferably a good solvent, and may be selected from at least one of N, N-dimethylformamide, N-dimethylacetamide, and dimethylsulfoxide, for example;
the concentration of the fused ring ligand in the solution is lower than that of the saturated solution of the fused ring ligand, and may be, for example, 2 to 10 mg/ml, such as 6.67 mg/ml.
The poor solvent can be at least one of methanol, ethanol, acetone, tetrahydrofuran, chloroform, deionized water, acetonitrile, 1, 4-dioxane and ethyl acetate; preferably, the poor solvent is at least one of methanol, ethanol, acetone, deionized water and ethyl acetate.
The volume ratio of the poor solvent to the solution of the fused ring ligand is more than 1: 1; preferably, the volume ratio can be (1-8): 1; according to an exemplary embodiment of the invention, the volume ratio may be 4: 1.
According to the preparation method, the standing is performed at room temperature for 3-48 hours, preferably, for 3-24 hours; according to an exemplary embodiment of the invention, rest for 12 hours;
the centrifugation is high-speed centrifugation; preferably, the centrifugal rotating speed is 10000-20000 revolutions per minute; for example, centrifugation is carried out at 12000 rpm for 3 minutes.
The invention also provides a preparation method of the micro-nano hydrogen bond organic framework material, which comprises the following steps: and adding a poor solvent into the solution of the condensed ring ligand under the stirring condition by adopting a recrystallization method, centrifuging and cleaning to obtain the micro-nano hydrogen bond organic framework material constructed based on the condensed ring ligand.
According to the invention, the preparation method of the micro-nano hydrogen bond organic framework material specifically comprises the following steps: adding deionized water or ethyl acetate into the solution of the condensed ring ligand under the stirring condition by adopting a recrystallization method, keeping stirring for a period of time, then adding ethanol, centrifuging at high speed, and cleaning for multiple times to obtain the micro-nano hydrogen bond organic framework material constructed based on the condensed ring ligand.
According to the preparation method of the present invention, the solvent in the solution of the fused ring ligand is a solvent in which the fused ring ligand can be dissolved, and is preferably a good solvent, and may be selected from at least one of N, N-dimethylformamide, N-dimethylacetamide, and dimethylsulfoxide, for example;
the concentration of the fused ring ligand in the solution is lower than that of the saturated solution of the fused ring ligand, and may be, for example, 2 to 10 mg/ml, such as 6.67 mg/ml.
According to the preparation method, the volume ratio of the solution of the condensed ring ligand, deionized water or ethyl acetate to ethanol can be 3-6: 10-40; for example, the ratio of the total weight of the components can be 3:20: 15-20; illustratively, the volume ratio may be 3:20:18, 3:20: 16.66.
Stirring for a period of 5-20 minutes; for example, stirring for 5 minutes, 10 minutes, 15 minutes;
the rotating speed of the high-speed centrifugation is 10000-20000 revolutions per minute; for example, centrifugation at 12000 rpm for 15 min;
the multiple cleaning is to respectively use ethanol and acetone for 3-5 times; for example, the washing with ethanol is performed 4 times, and then the washing with acetone is performed 4 times.
According to the preparation method, the particle size of the micro-nano material is 200 nanometers to 10 micrometers.
A pharmaceutical composition comprises the hydrogen bond organic framework material and a drug loaded on the material.
The invention also provides application of the hydrogen bond organic framework material in preparation of medicines. Preferably, the anticancer drug is loaded in the material, so as to realize the photodynamic-chemotherapy synergistic treatment.
Preferably, the drug is an anti-cancer drug.
Preferably, the anticancer drug may be one or more of doxorubicin, camptothecin, cisplatin, etc. or their derivatives.
The invention also provides a regeneration method of the hydrogen bond organic framework material, which comprises the step of treating the hydrogen bond organic framework material for 12-60 hours, such as 24-48 hours, by using acid (such as concentrated hydrochloric acid). Preferably, the treatment is soaking or dipping.
The invention has the beneficial effects that:
the invention utilizes the synergistic effect of multiple hydrogen bonds and the pi-pi interaction force of the condensed ring ligand to obtain the hydrogen bond organic framework material constructed based on the condensed ring ligand, and the organic framework material has the characteristics of high specific surface area, permanent pore channel, high chemical and thermal stability, mild synthesis conditions, excellent singlet oxygen generation capacity and the like, and solves the problems that the conventional hydrogen bond organic framework material has poor stability and can not maintain the permanent pore channel. The material is simple in preparation method and strong in operability, and the particle size of the particles can be freely controlled and can reach 200 nanometers as the minimum.
The material has good biocompatibility and lower biotoxicity, has excellent composite chemical-photodynamic treatment capacity after being further compounded with anticancer drugs, and the hydrogen bond organic framework material shows excellent cancer treatment effect and low cancer cell survival rate due to the coordination effect of the two.
Drawings
FIG. 1 is a schematic structural diagram of a hydrogen bonding organic framework material of the present invention, wherein: the middle pillar represents a channel in the structure.
FIG. 2 is a representation of the formula of fused ring ligands useful for preparing hydrogen bonded organic frameworks according to the present invention.
FIG. 3 is a comparison of XRD patterns of hydrogen bonded organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene prepared in example 1 and calculated simulations.
FIG. 4 is 77K N after different environmental treatments for hydrogen bonding organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene prepared in example 12And (4) adsorbing.
FIG. 5 is a comparative XRD pattern of hydrogen bonded organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene prepared in example 1 after different environmental treatments.
FIG. 6 shows the 77K N of hydrogen bonding organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene prepared in example 1 after different temperature treatment and acid environment repair2And (4) adsorbing.
FIG. 7 is a comparative XRD pattern of hydrogen bonded organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene prepared in example 1 after different temperature treatments.
FIG. 8 is an SEM image of hydrogen bonded organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene in different sizes prepared in example 3 (scale: 1 micron in a; scale: 300 nm in b; scale: 100 nm in c and d).
Fig. 9 is an SEM image of hydrogen bonded organic framework material loaded with doxorubicin prepared in example 5.
FIG. 10 is a singlet oxygen generation detection graph of the samples of example 1, example 3 and example 5.
FIG. 11 is a graph of in vitro cytotoxicity test of hydrogen bonding organic framework material loaded with doxorubicin prepared in example 5.
FIG. 12 is a graph of in vitro cell photodynamic therapy effect test of the hydrogen bonding organic framework material loaded with adriamycin prepared in example 5.
Detailed Description
The materials of the present invention, methods of making the same, and uses thereof, are described in further detail below with reference to specific examples. It is to be understood that the following examples are only illustrative and explanatory of the present invention and should not be construed as limiting the scope of the present invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Unless otherwise indicated, the raw materials and reagents used in the following examples are all commercially available products or can be prepared by known methods.
Part of the instrument information is as follows:
x-ray diffractometer: japanese chemistry Miniflex 600;
full-automatic specific surface and porosity analyzer: ASAP2020 and ASAP2460 by mack corporation;
scanning electron microscope: japanese electronic JSM 6700-F;
ultraviolet-visible spectrophotometer: shimadzu UV-2550.
Example 1 Hydrogen-bonded organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene
Preparation process of hydrogen bond organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene:
10 mg of 1,3,6, 8-tetra (p-carboxyphenyl) perylene was dissolved in 1.5 ml of N, N-dimethylformamide, and after the ligand was completely dissolved, 6 ml of methanol solution was added to the solution, and the mixture was stirred for 1 minute, after which the sample was allowed to stand at room temperature for 12 hours. And then centrifuging the mixture at 12000 r/min for 3 min, and continuously washing the mixture with acetone for 3 times to obtain the hydrogen-bond organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene. The material has a high specific surface area: calculated as 2122 m/g square according to the brunauer-Emmett-Teller formula, pore size 1.7 nm.
The material can be obtained after the mixture ratio of the materials is expanded by equal amount.
Example 2 Hydrogen bonding organic framework materials based on naphthalene, anthracene, phenalene, perylene
The preparation process of the hydrogen bond organic framework material based on naphthalene, anthracene, phenalene and perylene is the same as that of the embodiment, and only the raw materials need to be replaced by the specific compounds shown in fig. 2.
Example 3 micro-nano-scale hydrogen-bonding organic framework materials based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene
The preparation process of the nanoscale hydrogen bond organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene comprises the following steps: 10 mg of 1,3,6, 8-tetra (p-carboxyphenyl) pyrene was dissolved in 1.5 ml of N, N-dimethylformamide, and after the ligand was completely dissolved, 10 ml of deionized water was added to the solution at a stirring speed of 1000 rpm and the stirring was maintained for 5 minutes. Then, 9 ml of ethanol is added, the mixture is centrifuged at 12000 rpm for 15 minutes, and the mixture is washed by ethanol and acetone for 4 times in succession, so that the pyrene-based hydrogen bond organic framework material with the particle size of 200 nm is obtained (see fig. 8 d).
By changing the reaction time and conditions of synthesis, the hydrogen-bonding organic framework material from micron to nanometer can be obtained:
according to the preparation method of example 2, deionized water is changed into ethyl acetate, and hydrogen bonding organic framework material (shown in figure 8a) with the particle size of 10 microns and based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene is obtained;
according to the preparation method of example 2, after the stirring time is prolonged to 15min, the hydrogen bond organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene with the particle size of 1 micron is obtained (see figure 8 b);
according to the preparation method of example 2, after the stirring time is prolonged to 10min, the hydrogen bonding organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene with the particle size of 500 nm is obtained (see figure 8 c).
Example 4 micro-nano-scale Hydrogen bond organic framework materials based on naphthalene, anthracene, phenalene, and perylene
The preparation process of the nanoscale hydrogen bond organic framework material based on naphthalene, anthracene, phenalene and perylene is the same as that in example 2, and the hydrogen bond organic framework material based on naphthalene, anthracene, phenalene and perylene with the particle size of 200 nm can be obtained only by replacing the raw materials with the specific compound shown in fig. 2 and replacing the addition of ethanol with 8.33 ml.
By changing the reaction time and conditions of the synthesis (for example, by changing to a poor solvent with relatively weak polarity and prolonging the reaction time, a material with a larger relative diameter can be obtained), the hydrogen-bonding organic framework material from a micron scale to a nanometer scale can be obtained.
Example 5
Preparation of adriamycin-loaded nanoscale hydrogen bond organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene:
5 mg of the nano-sized hydrogen-bonded organic framework material based on 1,3,6, 8-tetra (p-carboxyphenyl) pyrene, prepared in example 2, was added to 2.5 ml of an aqueous doxorubicin solution containing 0.001 mol/l of dilute hydrochloric acid. Then, the solution containing the material is subjected to ultrasonic treatment in an ultrasonic machine for 2 minutes, then the solution is placed into a shaking table to shake for 1 hour at the speed of 240 revolutions per minute, then the solution is centrifuged at the speed of 12000 revolutions per minute for 15 minutes, and the solution is continuously washed with acetone for 2 times to obtain the nano hydrogen-bond organic framework material loaded with the adriamycin.
As can be seen from fig. 9: the hydrogen bond organic framework material loaded with the adriamycin still keeps the basic morphology, which shows that the stability is good.
Example 6 performance testing of hydrogen bonding organic framework materials prepared in example 1
Fig. 3 is a comparison graph of XRD obtained from the hydrogen bonding organic framework material prepared in example 1 and a calculation simulation.
And (3) testing conditions are as follows: the hydrogen bonding organic framework material prepared in example 1 was dried, and a powder XRD pattern was measured using the Miniflex 600 of japan at normal temperature and compared with the XRD pattern result obtained by calculation and simulation.
And (3) testing results: it is shown that the XRD diffraction peaks of the samples prepared in example 1 are highly fitted to the results obtained by computational simulation.
FIG. 4 is a drawing showing nitrogen absorption of the hydrogen bonding organic framework material prepared in example 1 after different environmental treatments.
And (3) testing conditions are as follows: example 1 the samples were tested 6 times with acetone exchange for 8 hours before vacuum drying at 90 degrees celsius for 6 hours before being subjected to 77K N2And (4) testing adsorption.
And (3) testing results: the result shows that the adsorption curve of the sample of example 1 is not changed significantly when the sample is soaked in deionized water, concentrated hydrochloric acid, 0.1M diluted hydrochloric acid, methanol or acetone for 117 days or soaked in boiling water for 10 days, which indicates that the structure is still stable at this time, and the hydrogen bond organic framework material has excellent chemical and thermal stability.
FIG. 5 is an XRD pattern of the hydrogen bonding organic framework material prepared in example 1 after different environmental treatments. The test result shows that: the XRD diffraction peak of the sample of example 1 is not changed after being soaked in deionized water, concentrated hydrochloric acid, 0.1M diluted hydrochloric acid, methanol or acetone for 117 days or soaked in boiling water for 10 days, which indicates that the structure of the sample still keeps stable. The hydrogen bond organic framework material has excellent chemical and thermal stability.
FIG. 6 shows the 77K N of the hydrogen bonding organic framework material prepared in example 1 after being treated at different temperatures and repaired in an acidic environment2And (5) absorbing the attached drawings.
And (3) testing conditions are as follows: the hydrogen bonding organic framework material prepared in example 1 was vacuum activated at 90 degrees celsius, 120 degrees celsius, 150 degrees celsius, 180 degrees celsius, and 210 degrees celsius, respectively, for 6 hours, followed by characterization of 77K nitrogen adsorption using ASAP2020 and ASAP2460 adsorbers from macco. Then, a part of the hydrogen bond organic framework material which is activated in vacuum for 6 hours at 210 ℃ is soaked in concentrated hydrochloric acid for 1 day, the other part of the hydrogen bond organic framework material which is used as a raw material is prepared and regenerated by the method of example 1, and 77K nitrogen adsorption is respectively carried out on the hydrogen bond organic framework material by using ASAP2020 and ASAP2460 adsorbers of Michco company.
And (3) testing results: the samples in example 1 are activated in vacuum for 6 hours at 90 ℃ and 120 ℃ respectively, and the adsorption curves of the samples are not obviously changed, which shows that the structures of the samples still keep stable. After the sample in the embodiment 1 is respectively activated in vacuum for 6 hours at 150 ℃, 180 ℃ and 210 ℃, the adsorption quantity of the adsorption curve is obviously reduced, which shows that a certain change occurs to the material framework at the temperature, and then the sample after high-temperature activation is soaked in concentrated hydrochloric acid for 1 day, the adsorption curve is restored to the original state, which shows that the framework is restored to the original state under the condition of the concentrated hydrochloric acid, and the sample has the self-restoring characteristic. Meanwhile, a sample after high-temperature activation is used as a raw material to prepare the hydrogen bond organic framework material, the adsorption curve of the material is basically consistent with the original adsorption curve, the frameworks of the material and the original adsorption curve are basically consistent, and the good reproducibility of the material is demonstrated.
Fig. 7 is an XRD pattern of the hydrogen bonding organic framework material prepared in example 1 after being treated at different temperatures. The test result shows that: after high-temperature treatment or restoration in an acidic environment, the powder XRD pattern of the hydrogen bond organic framework material is consistent with the simulated powder XRD pattern, which shows that the material still keeps a good framework structure and the crystal structure has no obvious phase change.
Example 7 singlet oxygen Generation Properties of Hydrogen bonding organic framework materials prepared in examples 1,3 and 5
And (3) testing conditions are as follows: 1.92 mg of the sample of example 1, the sample of example 3 and the sample of example 5 were added to 15 ml of a 0.32 mg/ml acetonitrile solution of 9, 10-diphenylanthracene subjected to an oxygen-charging operation for 30 minutes, respectively, and the ultraviolet-visible spectrum of the detection agent, 9, 10-diphenylanthracene, was measured under irradiation with a xenon lamp.
And (3) testing results: it can be seen from fig. 10 that the samples of example 1, example 3 and example 5 all had excellent singlet oxygen generation rates, and the performance of the samples of example 3 and example 5 was the best, next to that of the sample of example 1.
Example 8 in vitro cytotoxicity testing of doxorubicin-loaded hydrogen bonding organic framework materials prepared in example 5
And (3) testing conditions are as follows: hela cells were cultured in Gibco RPMI 1640 medium, inoculated in 96 wells for overnight culture, plated for 12h, treated with 1. mu.g/ml and 10. mu.g/ml of the samples of example 5 for 24 h, after removal of the treatment solution, tested in MTT assay, and the control group was tested using adriamycin solutions of different concentrations instead of the samples of example 5.
And (3) testing results: it can be seen from fig. 11 that the cells have good activity under the condition of no light and no sample, but after different samples are added, the cell survival rate of the experimental group added with anticancer drug adriamycin is obviously reduced, and when the adriamycin concentration reaches 10 micrograms/ml, the cell survival rate of the experimental group is only 10%, while under the same concentration condition, the cell survival rate of the experimental group of the samples of example 3 and example 5 is obviously higher, especially the cell survival rate of the experimental group added with the sample of example 5 can reach 75% under the condition that the sample concentration reaches 10 micrograms/ml, and such experimental results indicate that the sample of example 5 has lower cytotoxicity.
Example 9 in vitro cell photodynamic therapy efficacy test of hydrogen bonding organic framework material loaded with doxorubicin prepared in example 5
And (3) testing conditions are as follows: hela cells were cultured in Gibco RPMI 1640 medium, inoculated in 96 wells for overnight culture, plated for 12 hours, treated with 1. mu.g/ml, 10. mu.g/ml and 20. mu.g/ml of the samples of example 5 for 24 hours, removed from the treatment solution, irradiated with a 400 nm laser for 30 minutes, and then tested by MTT, and the control group was tested using adriamycin solutions of different concentrations and unloaded materials instead of the samples of example 5.
And (3) testing results: it can be seen from FIG. 12 that the survival rate of the cells of the different experimental groups was only 65% under the condition of the light without adding the sample, which is the damage of the light to the cells. The experiment group added with the sample of the example 5 has obviously reduced cell survival rate compared with the experiment group added with the sample of the example 3 when different samples are added under the illumination condition, and even the experiment group added with the sample of the example 5 can be close to the experiment group only added with the adriamycin when the addition concentration of the sample reaches 10 micrograms/milliliter, which shows that the sample of the example 5 has good cancer treatment effect.
The embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (30)
1. A hydrogen bonded organic framework material comprising fused ring ligands selected from the group consisting of structures represented by the following formulae:
the particle size of the material is 200 nanometers to 50 micrometers.
2. The hydrogen bonding organic framework material of claim 1, wherein the fused ring ligands are selected from 1-hydro-2, 5, 8-phenalene tricarboxylic acid, 1,3,6, 8-tetra (p-carboxyphenyl) pyrene, 2,5,8, 11-perylene tetracarboxylic acid, 2,5,8, 11-tetra (p-carboxyphenyl) perylene.
3. The hydrogen bonding organic framework material according to claim 1 or 2, wherein the particle size of the material is 200 nm to 30 μm.
4. The hydrogen bonding organic framework material of claim 3, wherein the particle size of the material is between 200 nanometers and 5 microns.
5. A method of making a hydrogen bonding organic framework material as claimed in any of claims 1 to 4, characterized in that the method comprises: and adding a poor solvent into the solution of the condensed ring ligand by adopting a recrystallization method, and fully stirring, standing, centrifuging and cleaning to obtain the hydrogen bond organic framework material constructed based on the condensed ring ligand.
6. The production method according to claim 5, wherein the solvent in the solution of the fused ring ligand is a solvent in which the fused ring ligand is soluble.
7. The production method according to claim 6, wherein the solvent in the solution of the fused ring ligand is a good solvent in which the fused ring ligand can be dissolved.
8. The method according to claim 7, wherein the solvent in the solution of the fused ring ligand is at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylacetamide, and dimethylsulfoxide.
9. The method of claim 5, wherein the concentration of the solution of fused ring ligands is less than the concentration of the saturated solution of fused ring ligands.
10. The method according to claim 5, wherein the poor solvent is at least one selected from the group consisting of methanol, ethanol, acetone, tetrahydrofuran, chloroform, deionized water, acetonitrile, 1, 4-dioxane, and ethyl acetate.
11. The method according to claim 10, wherein the poor solvent is at least one selected from methanol, ethanol, acetone, deionized water, and ethyl acetate.
12. The production method according to claim 5, wherein the volume ratio of the poor solvent to the solution of the condensed ring ligand is 1:1 or more.
13. The method according to claim 12, wherein the volume ratio of the poor solvent to the solution of the condensed ring ligand is (1-8): 1.
14. The method according to any one of claims 5 to 13, wherein the standing is performed at room temperature for 3 to 48 hours.
15. The method according to claim 14, wherein the standing is performed at room temperature for 3 to 24 hours.
16. The method of any one of claims 5-13, wherein the centrifugation is high speed centrifugation.
17. The method of claim 16, wherein the centrifugation speed is 10000-20000 rpm.
18. A method of making a hydrogen bonding organic framework material as claimed in any of claims 1 to 4, characterized in that the method comprises: and adding a poor solvent into the solution of the condensed ring ligand under the stirring condition by adopting a recrystallization method, centrifuging and cleaning to obtain the micro-nano hydrogen bond organic framework material constructed based on the condensed ring ligand.
19. The method of manufacturing according to claim 18, comprising: adding deionized water or ethyl acetate into the solution of the fused ring ligand under stirring by adopting a recrystallization method, continuously stirring, adding ethanol, centrifuging at a high speed, and cleaning for multiple times to obtain the micro-nano hydrogen bond organic framework material constructed based on the fused ring ligand.
20. The method of claim 19,
the solvent in the solution of the fused ring ligand is a solvent capable of dissolving the fused ring ligand;
the concentration of the solution of the fused ring ligand is lower than that of the saturated solution of the fused ring ligand;
the volume ratio of the solution of the condensed ring ligand, deionized water or ethyl acetate to ethanol is 3-6: 10-40;
continuously stirring for 5-20 minutes;
the rotating speed of the high-speed centrifugation is 10000-20000 revolutions per minute;
the multiple cleaning is to respectively use ethanol and acetone for 3-5 times;
the particle size of the micro-nano material is 200 nanometers to 10 micrometers.
21. The production method according to claim 20, wherein the solvent in the solution of the condensed ring ligand is a good solvent in which the condensed ring ligand is dissolved.
22. The method according to claim 21, wherein the solvent in the solution of the fused ring ligand is at least one selected from the group consisting of N, N-dimethylformamide, N-dimethylacetamide, and dimethylsulfoxide.
23. The method according to claim 21, wherein the concentration of the fused ring ligand in the solution is 2 to 10 mg/ml.
24. A pharmaceutical composition comprising the hydrogen bonding organic framework material of any one of claims 1 to 8 and a drug loaded on the material.
25. Use of the hydrogen bonding organic framework material of any of claims 1 to 4 in the manufacture of a medicament, said medicament being an anti-cancer drug.
26. The use of claim 25, wherein the drug is one or more of doxorubicin, camptothecin, cisplatin, or a derivative thereof.
27. The method for regenerating a hydrogen bonding organic framework material as claimed in any one of claims 1 to 4, comprising treating the hydrogen bonding organic framework material with an acid for more than 12 hours.
28. The regeneration process of claim 27, wherein the acid is concentrated hydrochloric acid.
29. The regeneration process according to claim 27, wherein the treatment time is 24 to 48 hours.
30. Regeneration process according to any one of claims 27 to 29, characterised in that the treatment is soaking or impregnation.
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