CN112007170A - Immunologic adjuvant functionalized metal organic framework material and preparation method and application thereof - Google Patents
Immunologic adjuvant functionalized metal organic framework material and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses an immunoadjuvant functionalized metal organic framework material, and a preparation method and application thereof, wherein the preparation process comprises the step of synthesizing MIL-101-NH2Namely MOF, ICG and MOF are combined into MOF-ICG, and MOF-ICG is loaded with CpG; the material can be applied to the preparation of medicines. Advantages of the invention include (1) UV-VISIBILITY of the materials provided by the inventionThe absorption spectrum peak value is positioned around near infrared light, the near infrared laser with single wavelength can be used for exciting the photodynamic and photothermal effect at the same time, and the nano-structure has excellent singlet oxygen generation capacity and photothermal conversion capacity under the irradiation of the near infrared laser, and has great application potential in the aspect of tumor phototherapy. (2) In a tumor microenvironment, CpG loaded by the material and TAA released by photodynamic and photothermal therapy jointly activate an immune system, enhance tumor cytotoxicity and improve treatment effect. (3) The material provided by the invention has the functions of tumor multi-modal imaging (fluorescence, photoacoustic, photothermal and nuclear magnetic resonance), and can be used for monitoring the tumor position and the treatment effect.
Description
Technical Field
The invention relates to the technical field of photodynamic and photothermal treatment carriers, in particular to preparation and application of an immunologic adjuvant functionalized material.
Background
Photodynamic and photothermal therapy is receiving increasing attention in the field of tumor therapy as a promising treatment. In recent years, various nano-carrier systems greatly improve the bioavailability and tumor enrichment rate of photosensitive molecules, but still have problems such as potential toxicity, low photosensitive drug loading efficiency, high early release rate and the like. The reason is that the introduced carrier material has long degradation period and even can not be degraded, the loading of the photosensitive drug is limited to non-covalent interaction, and no covalent interaction force is introduced, so that the stability of the carrier system is greatly reduced. The metal organic framework material with good biocompatibility and degradability is used for loading the photosensitizer, and the photosensitizer and the metal organic framework material are covalently combined, so that the loading efficiency and potential toxicity of the photosensitizer can be effectively improved. In addition, in order to improve the immune response rate, the introduction of the immune adjuvant can effectively stimulate the immune system and improve the treatment effect.
The metal organic framework material is taken as a research object, a photosensitizer and an immunologic adjuvant are loaded, a novel nano drug-carrying system is developed, multi-modal imaging and high-efficiency photodynamic and photothermal treatment modes of tumors are realized, and the method has a wide prospect of loading the immunologic adjuvant to improve the response rate of the tumors.
Disclosure of Invention
The object of the present invention is to provideCovalent loading photosensitizer indocyanine green (ICG) and porous electrostatic adsorption immunological adjuvant cytosine guanine dinucleotide (CpG) nano iron carboxylate metal organic framework (MIL-101-NH)2) The material (ICG-CpG @ MOF) can be passively targeted to a tumor part through an EPR effect, so that tumor multi-mode imaging (fluorescence, optoacoustic, photothermal and nuclear magnetic resonance) is realized, two treatment modes of photodynamic and photothermal can be realized simultaneously, the CpG and a tumor antigen (TAA) released by treatment can effectively activate an immune system, and the killing effect of tumor cells is enhanced.
Another object of the present invention is to provide a process for the preparation of the ICG-CpG @ MOF material described above;
in order to achieve the purpose, the invention adopts the following technical scheme:
the ICG-CpG @ MOF material takes a nano iron carboxylate metal organic framework (MIL-101-NH2) as a core, and is covalently connected with a photosensitizer ICG and a porous electrostatic adsorption immunoadjuvant CpG. The preparation process comprises the following steps: synthesis of MIL-101-NH2Namely MOF, ICG and MOF are combined to form MOF-ICG, and the MOF-ICG is loaded with CpG.
Further, the process of synthesizing MOFs comprises:
(1) separately dissolving 2-aminoterephthalic acid and FeCl3·6H2O；
(2) Adding the two liquids obtained in the step (1) into a high-pressure kettle for high-temperature mixing treatment;
(3) centrifuging the liquid obtained in the step (2), and removing the supernatant to collect precipitate to obtain precipitated powder;
(4) washing the precipitated starch powder;
(5) and drying the washed powder to obtain the product MOF.
Further, the detailed process of synthesizing MOFs is:
(1) 375mg of 2-aminoterephthalic acid and 1125mg of FeCl3·6H2O is dissolved in 12.5ml of dimethylformamide respectively;
(2) putting the two liquids in the step (1) into a 50ml stainless steel autoclave, and treating the mixture at 120 ℃ for 24 hours;
(3) centrifuging the liquid obtained in the step (2) at 8000rpm for 10 minutes, discarding the supernatant, and collecting the precipitate to obtain precipitated powder;
(4) washing the precipitated powder in the step (3) with dimethylformamide and ethanol for 3 times in sequence;
(5) vacuum drying the washed powder of (4) at 50 deg.C for 8 hr to obtain MIL-101-NH2(MOF)。
Further, the process of the ICG binding to MOF-ICG is:
(1) activating carboxyl of ICG-COOH;
(2) adding MOF into the mixture obtained in the step (1), and stirring;
(3) and (3) centrifuging the liquid in the step (2), discarding the supernatant, and recovering the precipitate to obtain the MOF-ICG combined product of ICG and MOF.
Further, the detailed process of the ICG binding to MOF-ICG is:
(1) 100mM, 10. mu.L EDC and 100mM, 10. mu.L NHS were added to 10mM, 200. mu.L ICG-COOH solution and the mixture was sonicated for 30 minutes to ensure thorough mixing, the purpose of this step being to activate the carboxyl groups;
(2) adding 10mg/mL,1mL MOF to the mixture of (1), and stirring at room temperature for 24 hours;
(3) centrifuging the liquid obtained in the step (2) at 8500 rpm for 10 minutes, discarding the supernatant, and recovering the precipitate to obtain a product of ICG and MOF combination, namely MOF-ICG.
Further, the MOF-ICG CpG-loading process is as follows:
(1) adding MOF-ICG to ultrapure water and suspending it using sonication;
(2) dissolving CpG in the solution in the step (1), and stirring at room temperature for 0.5 hour;
(3) and (3) centrifuging the solution obtained in the step (2), discarding the supernatant, and recovering and precipitating to obtain the CpG-loaded MOF-ICG which is expressed as ICG-CpG @ MOF.
Further, the detailed process of MOF-ICG CpG loading is as follows:
(1) 1.2mg of MOF-ICG was added to 1ml of ultrapure water and suspended using sonication;
(2) dissolving 84. mu.g of CpG in the solution of (1), and stirring at room temperature for 0.5 hour;
(3) the solution obtained in (2) was centrifuged at 8500 rpm for 10 minutes, the supernatant was discarded, and the MOF-ICG precipitated as a CpG-loaded fragment was recovered as ICG-CpG @ MOF.
The third object of the present invention is to provide the use of the ICG-CpG @ MOF material described above for the preparation of a medicament, in particular for the preparation of a medicament for photodynamic and photothermal therapy.
The light immunotherapy principle of the invention is as follows: in tumor phototherapy, the ICG-CpG @ MOF material enters tumor cells through macropinocytosis, the loaded ICG can absorb near infrared light and convert the near infrared light into heat energy, and a photosensitizer can be excited in the early stage of illumination under illumination to play a photodynamic treatment effect; with the extension of the illumination time, the photothermal effect of the ICG plays a role, and the synergistic phototherapeutic is realized. Photodynamic and photothermal therapeutic effects can destroy tumor cells, resulting in the release of tumor cell antigens (TAAs). The released TAA and CpG loaded by the material activate an immune system together, so that the effect of killing tumor cells is obviously enhanced, and the treatment effect is improved.
Has the advantages that: (1) the ultraviolet-visible absorption spectrum peak value of the material provided by the invention is positioned around near infrared light, the near infrared laser with single wavelength can be used for simultaneously exciting the photodynamic and photothermal effects, and the material has excellent singlet oxygen generation capacity and photothermal conversion capacity under the irradiation of the near infrared laser, and has huge application potential in the aspect of tumor phototherapy. (2) In a tumor microenvironment, CpG loaded by the material and TAA released by photodynamic and photothermal therapy jointly activate an immune system, enhance tumor cytotoxicity and improve treatment effect. (3) The material provided by the invention has the functions of tumor multi-modal imaging (fluorescence, photoacoustic, photothermal and nuclear magnetic resonance), and can be used for monitoring the tumor position and the treatment effect.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principles of the invention:
FIG. 1 is a schematic representation of the technical scheme for ICG-CpG @ MOF materials and their use.
FIG. 2 is a schematic diagram of the synthesis and application of ICG-CpG @ MOF material. A schematic synthesis of icg-CpG @ MOF; B. the multi-modal imaging (photoacoustic, nuclear magnetism and fluorescence imaging) guides a mechanism of the synergetic tumor photoimmunotherapy, ICG-CpG @ MOF is enriched in tumor tissues through an EPR effect, and 808nm laser activates photoimmunotherapy.
FIG. 3 is a graph showing the results of the characterization of ICG-CpG @ MOF material. A. Observing the morphology of the MOF by using a transmission electron microscope; B. observing the morphology of the MOF by a scanning electron microscope; particle size before and after mof modification; a bright field TEM image and an element mapping spectrum in STEM mode of ICG-CpG @ MOF; fourier transform infrared spectroscopy (FT-IR) of icg @ MOF; zeta potential before and after mof modification; ultraviolet absorption spectra of icg @ MOF and MOF alone.
FIG. 4 time-dependent internalization of FAM-ICG-CpG @ MOF by tumor cells. A. Imaging tumor cell internalization ICG-CpG @ MOF using confocal microscopy; B. flow cytometry examined the internalization efficiency of ICG-CpG @ MOF.
FIG. 5 photo-thermal and photodynamic effects of ICG-CpG @ MOF. Temperature imaging of icg-CpG @ MOF at different power densities (under 808nm laser illumination); increased temperature in an aqueous icg-CpG @ MOF solution (1mL) at different power densities by a 808nm laser; photothermal conversion stability of icg-CpG @ MOF (100 ° f g/mL); D. fluorescence microscopy detected ROS levels, (-) indicated no laser treatment and (+) indicated laser treatment; E. flow cytometry detection of ROS levels (-) indicates no laser treatment, (+) indicates laser treatment; F. detecting the effect of ICG-CpG @ MOF on apoptosis by flow cytometry; G. the effect of ICG-CpG @ MOF on apoptosis was examined by fluorescence microscopy.
FIG. 6. effect of ICG-CpG @ MOF on immune cell differentiation. The regulation and control effect of MOF on peritoneal macrophages; B. peritoneal macrophage CD80 expression analysis; the regulation and control effect of ICG-CpG @ MOF on spleen adherent cells; D. splenic adherent cell CD80 expression assay; E. effect of photothermal treatment on expression of splenic T cells CD4 and CD 8.
FIG. 7 multimodal imaging functionality of ICG-CpG @ MOF. A. Tumor near-infrared fluorescence in-situ imaging after tail vein injection; B. tumor in-situ near-infrared fluorescence imaging is carried out 24 hours after tail vein injection; C. the distribution of ICG-CpG @ MOF in each organ after 6h of tail vein injection; D. in-situ photothermal imaging; nuclear magnetic horizontal section (E) and coronal section (F) of tumor-bearing mice; G. photoacoustic imaging of tumors before and after in situ injection; H. PA images of ICG-CpG @ MOF solutions at different concentrations in vitro (0, 0.5, 1, 2, 5, and 10. mu.g/mL, respectively).
FIG. 8 in vivo therapeutic effect of ICG-CpG @ MOF. A. Tumor volume changes before and after treatment; B. statistical analysis of tumor volume; C. the therapeutic effect of lung metastasis; D. tumor and organ H & E staining before and after treatment in tumor-bearing mice.
Detailed Description
The present invention will be described in detail with reference to the drawings and specific embodiments, which are illustrative of the present invention and are not to be construed as limiting the present invention.
FIG. 1 is a schematic diagram of an ICG-CpG @ MOF material and a technical scheme for its use, the details of which are illustrated by the following specific examples.
Example Synthesis of ICG-CpG @ MOF Material
The synthetic ICG-CpG @ MOF material mainly comprises 3 parts: synthesis of MIL-101-NH2(MOF), ICG and MOF are combined into MOF-ICG, and the MOF-ICG is loaded with CpG.
MIL-101-NH2The (MOF) synthesis procedure was as follows:
(1) 375mg of 2-aminoterephthalic acid and 1125mg of FeCl3·6H2O is dissolved in 12.5ml of dimethylformamide respectively;
(2) putting the two liquids in the step (1) into a 50ml stainless steel autoclave, and treating the mixture at 120 ℃ for 24 hours;
(3) centrifuging the liquid obtained in the step (2) at 8000rpm for 10 minutes, discarding the supernatant, and collecting the precipitate to obtain precipitated powder;
(4) washing the precipitated powder in the step (3) with dimethylformamide and ethanol for 3 times in sequence;
(5) vacuum drying the washed powder of (4) at 50 deg.C for 8 hr to obtain MIL-101-NH2(MOF)。
ICG binding to MOF:
(6) EDC (100mM, 10. mu.L) and NHS (100mM, 10. mu.L) were added to the ICG-COOH (10mM, 200. mu.L) solution and the mixture was sonicated for 30 minutes to ensure adequate mixing, the purpose of this step being to activate the carboxyl groups;
(7) adding the MOF obtained in (5) (10mg/mL,1mL) to the mixture in (6), and stirring at room temperature for 24 hours;
(8) centrifuging the liquid obtained in the step (7) at 8500 rpm for 10 minutes, discarding the supernatant, and recovering the precipitate to obtain an ICG and MOF combined product (MOF-ICG).
MOF-ICG Loading CpG:
(9) 1.2mg of MOF-ICG was added to 1ml of ultrapure water and suspended using sonication;
(10) CpG (84. mu.g) was dissolved in the solution described in (9) and stirred at room temperature for 0.5 hours;
(11) the solution obtained in (10) was centrifuged at 8500 rpm for 10 minutes, the supernatant was discarded, and the precipitate was recovered as CpG-loaded MOF-ICG (denoted as ICG-CpG @ MOF). The synthetic schematic diagram is shown in FIG. 2A; the technical route of application of ICG-CpG @ MOF is shown in figure 1, and the principle of photo-immunotherapy is shown in figure 2B; the characterization results of the synthesized materials are shown in fig. 3. The results of experiments relating to time-dependent internalization of FAM-ICG-CpG @ MOF by tumor cells are shown in FIG. 4.
Example two photodynamic and photothermal effects of ICG-CpG @ MOF materials
(1) Dissolving the ICG-CpG @ MOF material in deionized water to ensure that the concentration of the ICG-CpG @ MOF material in a system is 100 mug/mL; placing the solution at 0.5, 1.0, 1.5, 2W/cm2Irradiating for 0-5 minutes under near infrared laser with wavelength of 808nm, and recording temperature change; as shown in FIG. 5, the temperature of the material gradually rises within 5min, and after 5min, the temperature reaches a stable level and is maintained at a higher level, which proves that the material has better photothermal conversion capability. Furthermore, as shown in FIG. 5C, ICG-CpG @ MOF can replicate well in response to photothermal conversion induced by a 808nm laser (1.5W/cm 2). The latter experiment was irradiated with a 808nm laser (1.5W/cm2) for 5 min.
(2) To examine the photodynamic effect of the material, ICG-CpG @ MOF material (final concentration 20nM, the same final concentration for the following cell assay) was incubated with 4T1 tumor cells, as shown in fig. 4, over a period of time, the proportion of material entering the cells increased with time, the cells were then incubated with a commercially available active oxygen probe (DCFH-DA), and the cell system was exposed to 1.5W/cm2 of near infrared laser at 808nM wavelength to measure the intensity of the fluorescence signal from the solution; as shown in FIG. 5D, the laser-irradiated group alone slightly increased intracellular ROS levels, and the fluorescence intensity of the ICG-CpG @ MOF + laser group was significantly increased. Flow cytometry to detect ROS levels as in fig. 5 e; the effect of ICG-CpG @ MOF on apoptosis was examined by fluorescence microscopy as shown in figure 5g. It can be seen that the ROS level of the cells is increased and the apoptosis rate is obviously increased after the laser treatment of ICG-CpG @ MOF +.
Example killing of 4T1 tumor cells by the TriICG-CpG @ MOF Material
Inoculating 4T1 cells in logarithmic growth phase to a 6-hole culture plate, culturing overnight, and after the cells are completely attached to the wall, discarding the old culture medium, wherein the method comprises the following steps: and after corresponding grouping treatment is carried out on a control group, a single ICG-CpG @ MOF group, a single laser group and an ICG-CpG @ MOF + laser group, the apoptosis condition is detected by using a commercially available apoptosis detection kit. The result is shown in fig. 5F, and it can be seen from the figure that the tumor cells of the single ICG-CpG @ MOF group and the single laser group have no significant change compared with the control group, and the apoptosis rate of the ICG-CpG @ MOF + laser group is significantly increased, which proves that the material has a better effect of promoting the apoptosis of the tumor cells in the phototherapy process.
Example four ICG-CpG @ MOF Material activation of immune cells
(1) Separating primary abdominal cavity macrophages of a mouse, setting a blank control group control, respectively co-culturing CpG, MOF and ICG-CpG @ MOF materials and the separated macrophages for 48 hours, and detecting the expression of CD80 and CD11c by flow cytometry. The results are shown in FIGS. 6A-B, and it can be seen from the figure that CpG and ICG-CpG @ MOF material can promote the expression of macrophages CD80 and CD11c, i.e. CpG and ICG-CpG @ MOF material has stronger activation effect on macrophages.
(2) Mouse spleen cells are separated, and after 4T1 cells, CpG, MOF, ICG-CpG @ MOF material and laser are respectively cocultured with spleen adherent cells or suspended T cells for 48 hours, the expression of CD80 and CD11c of the mouse spleen cells is detected by flow cytometry. As shown in FIGS. 6C and D, CpG promotes the expression of spleen adherent CD80 and CD11C, while 4T1 inhibits the expression of spleen adherent CD80 and CD 11C. As shown in FIG. 6E, the expression of T cell CD8 was significantly enhanced after the co-culture of ICG-CpG @ MOF and the residues after the laser treatment of the cells and the suspension T cells separated from the spleen, indicating that the ICG-CpG @ MOF material designed by the present invention has a good immune activation effect.
In addition, experiments relating to the effect of ICG-CpG @ MOF immunotherapy were also performed and the results are shown in FIG. 7.
EXAMPLE therapeutic Effect of the five ICG-CpG @ MOF materials on tumor-bearing mice
(1) Bal B/C mice (4-6 weeks) were used as experimental animals and inoculated with 1 x 1064T1 cells were used to construct a subcutaneous tumor model, which was randomized into 3 groups when the tumor diameter was approximately 8 mm: PBS group, ICG-CpG @ MOF group and ICG-CpG @ MOF + laser group, the dosage of ICG-CpG @ MOF is 25mg/kg, the same dosage is used in the following animal experiments, and the tumor size of each group is observed. The results are shown in fig. 8A and B, the ICG-CpG @ MOF + laser group forms target tumor lesions on the 7 th day, the tumor lesions basically disappear on the 21 th day, and the experimental results show that the ICG-CpG @ MOF material designed by the invention has good tumor killing effect compared with other groups.
(2) Bal B/C mice (4-6 weeks) as experimental animals, 1 x 1064T1 cells were injected into the mouse tail vein in order to model 4T1 metastases. Mice were randomized into 3 groups: PBS control group, ICG-CpG @ MOF group and ICG-CpG @ MOF + LASER group. The results are shown in FIG. 8C, and 21 days after tumor cell injection, the tumor cells of PBS control group infiltrated the whole lung of the mouse, while the tumor of ICG-CpG @ MOF + laser group was significantly inhibited. In order to detect the histocompatibility of the material and the influence on each organ, each group of tumor-bearing mouse tissues is subjected to H&And E, dyeing. The results are shown in FIG. 8D, in which ICG-CpG @ MOF + laser group tumor cells exhibited vacuolization, H, compared to the PBS control group&E No obvious lesion was observed in each organ stained. The ICG-CpG @ MOF material designed by the invention has a good metastatic tumor killing effect, has no obvious damage to each organ, and has good biocompatibility.
Example six ICG-CpG @ MOF Material Multi-modality imaging functionality
(1) Bal B/C mice (4-6 weeks) were used as experimental animals and inoculated with 1 x 1064T1 cells were used to construct a subcutaneous tumor model, and the effect of fluorescence imaging of the material was evaluated after tail vein injection of ICG-CpG @ MOF when the tumor diameter was about 8 mm. As a result, as shown in FIG. 7A, fluorescence was detected at the tumor site 1 hour after the injection of the materialSignal, and the signal gradually increased over 6 hours. The distribution of ICG-CpG @ MOF in each organ 6h after tail vein injection is shown in FIG. 7C; the fluorescence intensity 24 hours after the injection of the material was analyzed by using a multifunctional near-infrared scanner (to avoid the fluorescence interference of the organ site), and the results are shown in fig. 7B, and the tumor site still detected strong fluorescence signals at 24 hours, indicating that the ICG-CpG @ MOF material has a good fluorescence imaging function.
(2) Bal B/C mice (4-6 weeks) were used as experimental animals and inoculated with 1 x 1064T1 cells were used to construct a subcutaneous tumor model, which was randomized into 3 groups when the tumor diameter was approximately 8 mm: the system comprises a laser group, an ICG @ MOF group and an ICG @ MOF + laser group, wherein the photothermal imaging result is evaluated by an infrared thermal imager after the groups are processed. The results are shown in FIG. 7D, which shows good photothermographic results for the ICG @ MOF + laser group after material injection.
(3) Bal B/C mice (4-6 weeks) were used as experimental animals and inoculated with 1 x 1064T1 cells were used to construct a subcutaneous tumor model, which was randomized into 2 groups when the tumor diameter was approximately 8 mm: PBS control group, ICG-CpG @ MOF group, and the effect of MRI was evaluated after each group was treated. The results are shown in FIGS. 7E-F, and the ICG-CpG @ MOF material can significantly improve the nuclear magnetic imaging effect of the tumor site.
(4) Bal B/C mice (4-6 weeks) were used as experimental animals and inoculated with 1 x 1064T1 cells are used for constructing a subcutaneous tumor model, when the diameter of the tumor is about 8mm, photoacoustic signals of the tumor are detected before and 6 hours after the ICG-CpG @ MOF material is injected, and the photoacoustic imaging effect of the material is evaluated. The results are shown in FIGS. 7G-H, where there is a strong photoacoustic signal 6 hours after the material was injected, indicating that the ICG-CpG @ MOF material has good photoacoustic imaging function.
The technical solutions provided by the embodiments of the present invention are described in detail above, and the principles and embodiments of the present invention are explained herein by using specific examples, and the descriptions of the embodiments are only used to help understanding the principles of the embodiments of the present invention; meanwhile, for a person skilled in the art, according to the embodiments of the present invention, there may be variations in the specific implementation manners and application ranges, and in summary, the content of the present description should not be construed as a limitation to the present invention.
Claims (10)
1. An immunoadjuvant functionalized metal organic framework material is characterized in that the material is a nano iron carboxylate metal organic framework MIL-101-NH which is covalently loaded with photosensitizer indocyanine green ICG and immunoadjuvant cytosine guanine dinucleotide CpG adsorbed by porous static electricity2The material, denoted ICG-CpG @ MOF.
2. A method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 1, wherein the method comprises the following steps:
the process comprises the following steps: synthesis of MIL-101-NH2Namely MOF, ICG and MOF are combined to form MOF-ICG, and the MOF-ICG is loaded with CpG.
3. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 2, wherein the method comprises the following steps:
the process for synthesizing the MOF comprises the following steps:
(1) separately dissolving 2-aminoterephthalic acid and FeCl3·6H2O；
(2) Adding the two liquids obtained in the step (1) into a high-pressure kettle for high-temperature mixing treatment;
(3) centrifuging the liquid obtained in the step (2), and removing the supernatant to collect precipitate to obtain precipitated powder;
(4) washing the precipitated starch powder;
(5) and drying the washed powder to obtain the product MOF.
4. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 3, wherein the method comprises the following steps:
the detailed process for the synthesis of MOFs is:
(1) 375mg of 2-aminoterephthalic acid and 1125mg of FeCl3·6H2O is dissolved in 12.5ml of dimethylformamide respectively;
(2) putting the two liquids in the step (1) into a 50ml stainless steel autoclave, and treating the mixture at 120 ℃ for 24 hours;
(3) centrifuging the liquid obtained in the step (2) at 8000rpm for 10 minutes, discarding the supernatant, and collecting the precipitate to obtain precipitated powder;
(4) washing the precipitated powder in the step (3) with dimethylformamide and ethanol for 3 times in sequence;
(5) vacuum drying the washed powder of (4) at 50 deg.C for 8 hr to obtain MIL-101-NH2(MOF)。
5. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 2, wherein the method comprises the following steps:
the process of the ICG binding to MOF-ICG is:
(1) activating carboxyl of ICG-COOH;
(2) adding MOF into the mixture obtained in the step (1), and stirring;
(3) and (3) centrifuging the liquid in the step (2), discarding the supernatant, and recovering the precipitate to obtain the MOF-ICG combined product of ICG and MOF.
6. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 5, wherein the method comprises the following steps:
the detailed process of the ICG binding to MOF-ICG is:
(1) 100mM, 10. mu.L EDC and 100mM, 10. mu.L NHS were added to 10mM, 200. mu.L ICG-COOH solution and the mixture was sonicated for 30 minutes to ensure thorough mixing, the purpose of this step being to activate the carboxyl groups;
(2) adding 10mg/mL,1mL MOF to the mixture of (1), and stirring at room temperature for 24 hours;
(3) centrifuging the liquid obtained in the step (2) at 8500 rpm for 10 minutes, discarding the supernatant, and recovering the precipitate as a product of the combination of ICG and MOF, namely MOF-ICG.
7. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 2, wherein the method comprises the following steps:
the MOF-ICG CpG-loading process is as follows:
(1) adding MOF-ICG to ultrapure water and suspending it using sonication;
(2) dissolving CpG in the solution in the step (1), and stirring at room temperature for 0.5 hour;
(3) and (3) centrifuging the solution obtained in the step (2), discarding the supernatant, and recovering and precipitating to obtain the CpG-loaded MOF-ICG which is expressed as ICG-CpG @ MOF.
8. The method for preparing an immunoadjuvant functionalized metal organic framework material according to claim 7, wherein the method comprises the following steps:
the detailed process of MOF-ICG CpG loading is as follows:
(1) 1.2mg of MOF-ICG was added to 1ml of ultrapure water and suspended using sonication;
(2) dissolving 84. mu.g of CpG in the solution of (1), and stirring at room temperature for 0.5 hour;
(3) the solution obtained in (2) was centrifuged at 8500 rpm for 10 minutes, the supernatant was discarded, and the MOF-ICG precipitated as a CpG-loaded fragment was recovered as ICG-CpG @ MOF.
9. Use of an immunoadjuvant functionalized metal organic framework material according to claim 1 for the preparation of a medicament.
10. Use of an immunoadjuvant functionalized metal organic framework material according to claim 1 or 9 for the preparation of a medicament for photodynamic and photothermal therapy.
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