CN115501337B - Liposome nano-particle and preparation method and application thereof - Google Patents
Liposome nano-particle and preparation method and application thereof Download PDFInfo
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- CN115501337B CN115501337B CN202211160735.1A CN202211160735A CN115501337B CN 115501337 B CN115501337 B CN 115501337B CN 202211160735 A CN202211160735 A CN 202211160735A CN 115501337 B CN115501337 B CN 115501337B
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
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- A61K49/0084—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form dispersion, suspension, e.g. particles in a liquid, colloid, emulsion liposome, i.e. bilayered vesicular structure
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Abstract
The invention discloses a liposome nanoparticle, and a preparation method and application thereof. The liposome nanoparticle is prepared from raw materials including a photosensitizer, a STING signal pathway agonist, a thermal phase change material and a lipid material; the photosensitizer is a near infrared two-region photosensitizer; the thermal phase change material is a combination of lauric acid and stearic acid; the lipid material is a combination of soybean lecithin and distearoyl phosphatidylethanolamine-polyethylene glycol. The nanoparticle has good physical and chemical properties, excellent imaging capability and killing effect on cancer cells, can optimize photo-thermal treatment, realizes accurate and efficient anti-tumor treatment of imaging guidance, and can overcome the application limitation caused by the problems of poor light tissue penetration, low imaging sensitivity, low selectivity on tumor tissues, easy recurrence after operation and the like in the field of tumor treatment of photo-thermal treatment.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a nanoparticle, a preparation method and application thereof.
Background
Current methods for treating cancer, such as chemotherapy, radiation therapy, immunotherapy, and surgery, are limited by various factors, such as accidental necrosis of healthy cells, immunological destruction, or development of secondary cancer. Among a plurality of treatment means, the photothermal treatment has the advantages of non-invasiveness, non-toxicity, short time, remarkable curative effect and the like, and the different temperatures can be controlled to cause different degrees of damage to tumors. Photothermal therapy is a therapeutic method that uses a material with high photothermal conversion efficiency, injects it into the interior of a human body, gathers near tumor tissue using a targeting recognition technique, and converts light energy into heat energy under irradiation of an external light source (typically near infrared light) to kill cancer cells. Gold nanoparticles, for example, have been approved by the FDA as photothermal agents for photothermal treatment of clinical pancreatic cancer. The development of photosensitizers has also gradually moved from the development of different materials in the lateral direction to the optimization of the performance of the photosensitizers themselves in the longitudinal direction. Such as better biocompatibility, higher light-to-heat conversion efficiency, etc. However, there are still some problems with photothermal therapy today that require further improvement.
(1) The accurate laser radiation of the photothermal therapy at the tumor part is critical for developing the photothermal therapy of the tumor, but the imaging sensitivity of the photothermal therapy is not high at present.
(2) Due to physical limitations of near infrared light penetrating through tissues, it cannot be incident into deep layers of organisms, so that research on internal deep tumors is lacking, and tumor cells outside an irradiation area can survive under photothermal treatment, thereby causing tumor recurrence and metastasis. This limitation results in the photothermal treatment stopping on superficial tumor types.
(3) The traditional photothermal treatment not only causes apoptosis of tumor cells, but also causes death of a large number of normal cells and immune cells in tumor tissues, thereby inducing metastasis and recurrence of the tumor.
(4) In the selection of treatment temperature, high temperature treatment (above 50 ℃) easily causes the damage of normal tissues around the tumor, and low temperature photothermal treatment (42 ℃ -46 ℃) easily causes poor treatment effect due to the expression of heat shock proteins in tumor cells.
Disclosure of Invention
Based on the above, the invention provides a novel liposome nanoparticle which has good physical and chemical properties, excellent imaging capability and killing effect on cancer cells, can optimize photo-thermal treatment, realize accurate and efficient anti-tumor treatment of imaging guidance, and can overcome the application limitation caused by the problems of poor light tissue penetration, low imaging sensitivity, low selectivity on tumor tissues, easy recurrence after operation and the like in the field of tumor treatment of photo-thermal treatment.
Specifically, the invention comprises the following technical scheme.
A liposome nanoparticle is prepared from raw materials including photosensitizer, STING signal channel agonist, thermal phase change material and lipid material;
the photosensitizer is a near infrared two-region photosensitizer;
the thermal phase change material is a combination of lauric acid and stearic acid;
the lipid material is a combination of soybean lecithin and distearoyl phosphatidylethanolamine-polyethylene glycol.
In some embodiments, the photosensitizer, STING signaling pathway agonist, thermal phase change material, and lipid material are in a mass ratio of 1:0.8-1.2:15-25:20-30.
In some embodiments, the photosensitizer, STING signaling pathway agonist, thermal phase change material, and lipid material are in a mass ratio of 1:0.9-1.1:18-22:23-27.
In some embodiments, the photosensitizer, STING signaling pathway agonist, thermal phase change material, and lipid material are in a mass ratio of 1:1:19-21:24-26.
In some embodiments, the photosensitizer has the structural formula:
in some of these embodiments, the STING signaling pathway agonist is 2, 5-pentoxifylline.
In some embodiments, the thermal phase change material has a mass ratio of 1-6:1 and stearic acid.
In some embodiments, the thermal phase change material has a mass ratio of 2-5:1 and stearic acid.
In some embodiments, the thermal phase change material has a mass ratio of 3-4:1 and stearic acid.
In some embodiments, the lipid material is in a mass ratio of 1-5:1 and distearoyl phosphatidylethanolamine-polyethylene glycol.
In some embodiments, the lipid material is in a mass ratio of 2-4:1 and distearoyl phosphatidylethanolamine-polyethylene glycol.
In some embodiments, the lipid material is in a mass ratio of 2.5-3.5:1 and distearoyl phosphatidylethanolamine-polyethylene glycol.
The invention also provides a preparation method of the liposome nano-particles, which comprises the following technical scheme.
The preparation method of the liposome nano-particles comprises the following steps:
(1) Dissolving the thermal phase change material in a solvent to obtain a solution of the thermal phase change material;
(2) Dissolving the lipid material in a solvent to obtain a liposome solution;
(3) Respectively dissolving the photosensitizer and the STING signal pathway agonist in a solvent to respectively obtain a photosensitizer solution and a STING signal pathway agonist solution;
(4) And mixing the solution of the thermal phase change material, the photosensitizer solution and the STING signal path agonist solution, dripping the mixture into the preheated liposome solution, performing ultrasonic treatment, and then placing the obtained mixed solution into ice water.
In some of these embodiments, the solvent of step (1) is tetrahydrofuran.
In some of these embodiments, the concentration of the thermal phase change material in the solution of the thermal phase change material is from 3mg/mL to 5mg/mL.
In some embodiments, the solvent of step (2) is a 3-5% aqueous ethanol solution.
In some of these embodiments, the concentration of the lipid material in the liposome solution is 0.5mg/mL to 1.5mg/mL.
In some of these embodiments, the solvent of step (3) is tetrahydrofuran.
In some of these embodiments, the photosensitizer solution and STING signaling pathway agonist solution are present at a concentration of 2mg/mL to 3mg/mL, respectively.
In some of these embodiments, the temperature of the pre-warmed liposome solution is 45 ℃ -55 ℃.
In some of these embodiments, the conditions of the ultrasound include: the frequency is 35-45KHZ, the time is 3-8 min, and the temperature is 20-35 ℃.
The invention also provides application of the liposome nanoparticle, which comprises the following technical scheme.
The liposome nano-particles are applied to the preparation of antitumor drugs.
The principle of the invention is as follows:
near infrared fluorescence two-region imaging has the advantages of high imaging sensitivity and high tissue penetrating capability, light is scattered after entering the tissue in principle, and the light scattering coefficient is monotonically reduced when the wavelength is longer, so that the near infrared two-region imaging has stronger penetration depth and photo-thermal effect on the tissue, and the generation of heat causes tissue swelling to generate ultrasonic waves, thereby providing a photoacoustic signal. Therefore, the near infrared two-region fluorescent dye can improve the limitations of photothermal treatment caused by tissue penetration and imaging sensitivity to a certain extent, and can well guide accurate photothermal treatment on living bodies. However, according to the mechanism by which photothermal therapy is effective, rapid tumor ablation is necessary in hyperthermia Wen Zaiguang, however, high temperatures also have a killing effect on normal cells and even immune cells beneficial against tumors without differentiating between me and me, and if the temperature is not reached, residual tumor cells are also susceptible to recurrence.
STING signaling (i.e., interferon stimulating factor) can protect cells from various pathogens by promoting anti-tumor immune responses, and has the effect of preventing cancer progression. This is an immune pathway for interferon expression activated by cytoplasmic DNA. Tumor cells have the characteristics of unstable genome, oxidative stress and vigorous metabolism. In these intense states, nuclear and mitochondrial DNA is fragile, easily destroyed, and leaked out. Thus, the use of the cGAS-STING pathway for the treatment of tumors is of great advantage.
Based on the problems, the liposome nano-particles with light and heat sensitivity are prepared by selecting specific thermal phase change materials and lipid materials to be matched with infrared two-region photosensitizers DTTB and STING signal channel agonists DMXAA, and the liposome nano-particles can combine the improved light and heat treatment with STING immune channels, so that the application scene of the light and heat treatment is greatly expanded. The liposome nano-particles can realize accurate photothermal therapy and controllable drug release under the guidance of near infrared fluorescence two regions, and realize accurate photothermal immune synergistic anti-tumor therapy. The liposome nanoparticle of the invention carries a near infrared two-region photosensitizer DTTB and a STING signal pathway agonist DMXAA, and under 808nm laser radiation, the photosensitizer DTTB plays a role in photothermal treatment to improve local temperature, so that tumor ablation is caused and immunogenic death (ICD) of tumor cells is induced, and a danger related molecular mode and tumor related antigens are released. Meanwhile, the liposome nano-particles have the characteristic of photo-thermal sensitivity, and have the thermal phase change property at about 42 ℃, so that the heat generated by photo-thermal treatment can crack the liposome nano-particles, release STING agonist, activate cGAS-STING signal path, induce tumor apoptosis, promote DC cell maturation, recruit T cells and trigger a strong adaptive anti-tumor immunity. The method utilizes immunotherapy to be accurately controlled by an organism, only kills tumor cells, and utilizes the immunotherapy to compensate the incompleteness of low-temperature photothermal therapy; simultaneously, the photothermal therapy can activate anti-tumor immune response by generating tumor antigen or immune related molecules from dead tumor cells, so that the tumor is converted from cold tumor to immunogenic heat tumor, and the combined action of the tumor antigen and the immune related molecules realizes the synergistic therapeutic effect of 1+1 to more than 2.
The liposome nanoparticle has the following beneficial effects:
the liposome nanoparticle has good physical and chemical properties, excellent imaging capability and killing effect on cancer cells, can optimize photothermal treatment, and realizes imaging guidance of accurate and efficient anti-tumor treatment. The liposome nanoparticle has good light tissue penetrating power, can be incident into the deep layer of an organism and is used for treating internal deep tumors, meanwhile, the liposome nanoparticle has an EPR effect, so that a photosensitizer can be more easily enriched at a tumor part, and meanwhile, tumor cells can be selectively killed by combined immunotherapy, so that the damage to normal cells is reduced. In addition, the liposome nanoparticle has a thermal phase transition property at about 42 ℃, and can release STING agonist at low temperature to play a role of immunotherapy, so that the liposome nanoparticle can achieve a good anti-tumor effect at low temperature, and the defect of tumor peripheral normal tissue injury caused by high-temperature treatment (more than 50 ℃) in photothermal treatment is overcome. Therefore, the liposome nanoparticle can overcome the application limitation caused by the problems of poor light tissue penetrating power, low imaging sensitivity, low selectivity on tumor tissues, easy recurrence after operation and the like in the field of tumor treatment of photo-thermal treatment, so that the photo-thermal treatment is more effective and more available.
Drawings
FIG. 1 is an endothermic peak of liposome nanoparticles tested using DSC differential scanning calorimeter.
Fig. 2 is a transmission electron microscope image of liposome nanoparticles.
FIG. 3 is a graph of particle size of liposome nanoparticles.
Fig. 4 is a graph of photoacoustic signals of liposome nanoparticles at different concentrations in vitro.
Fig. 5 is a graph of the quantification of photoacoustic signals from liposome nanoparticles at different concentrations in vitro.
Fig. 6 is a photoacoustic imaging experimental quantification of liposome nanoparticles in vivo.
Fig. 7 is a photo acoustic signal diagram of liposome nanoparticles in vivo.
FIG. 8 is a chromatogram of DMXAA released from liposome nanoparticles before and after illumination.
Fig. 9 is an electron microscope image of liposome nanoparticles before illumination.
Fig. 10 is an electron microscope image of the liposome nanoparticle after cooling again after illumination.
FIG. 11 shows the result of cytotoxicity of liposome nanoparticles on tumor cells, CCK-8.
FIG. 12 shows the result of cell death staining of tumor cells by liposome nanoparticles.
Fig. 13 is a cell flow apoptosis result of liposome nanoparticles on tumor cells.
Detailed Description
The technical scheme of the invention is further described by the following specific examples. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
The terms "comprising" and "having" and any variations thereof, are intended to cover a non-exclusive inclusion. For example, a process, method, apparatus, article, or device that comprises a list of steps is not limited to the elements or modules listed but may alternatively include additional steps not listed or inherent to such process, method, article, or device.
In the present invention, the term "plurality" means two or more. "and/or", describes an association relationship of an association object, and indicates that there may be three relationships, for example, a and/or B, and may indicate: a exists alone, A and B exist together, and B exists alone. The character "/" generally indicates that the context-dependent object is an "or" relationship.
The following are specific examples.
The infrared two-region photosensitizer DTTB used in the following examples has the structural formula:
EXAMPLE 1 preparation of Liposome nanoparticles (PLDD)
The liposome nanoparticle with thermal phase transition property at about 42 ℃ is synthesized by adopting a nano precipitation method, and the specific steps are as follows:
(1) Lauric acid and stearic acid (mass ratio of 3.5:1) were dissolved in tetrahydrofuran to prepare a hot phase change material solution having a total concentration of 4mg/mL of lauric acid and stearic acid.
(2) Soybean lecithin and distearoyl phosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG-2 k) (mass ratio 3:1) were dissolved in 4% ethanol aqueous solution by volume to prepare a liposome solution with a total concentration of 1mg/mL of soybean lecithin and DSPE-PEG-2 k.
(3) 3mL of liposome solution was heated to 50 ℃. 600uL of the hot phase-change material solution is taken, mixed with DTTB (48 uL,2.5mg/mL, dissolved in tetrahydrofuran) and 2, 5-pentoxifylline (DMXAA) (48 uL,2.5mg/mL, dissolved in tetrahydrofuran) which are required to be loaded, and then added dropwise into the preheated liposome solution, the mixture solution is subjected to ultrasonic treatment at room temperature and 40KHZ for 5min, then the mixed solution is immediately placed into ice water, so that liposome nano-drugs which are used for coating the two drugs are rapidly formed due to the hot phase-change effect and the hydrophobic drug loading effect of the liposome, after 2min, unencapsulated molecules and organic solvents are removed by concentration by an ultrafiltration centrifuge tube (Sartorius, MWCO=10 kDa), and after three times of washing by water, the synthesized liposome nano-particles are suspended in water for further use.
Example 2 physicochemical Property testing of Liposome nanoparticles
(1) The endothermic peaks of the liposome nanoparticles prepared with the different component materials were tested using a DSC differential scanning calorimeter.
The results are shown in FIG. 1: wherein LA: sa=3.5:1 represents the liposome nanoparticle prepared in example 1; LA represents a liposome nanoparticle prepared as in example 1, substituting lauric acid and stearic acid in a mass ratio of 3.5:1 with lauric acid; SA represents the liposome nanoparticle prepared as in example 1, substituting stearic acid for lauric acid and stearic acid in a mass ratio of 3.5:1. As can be seen from the results of fig. 1, when LA: when sa=3.5:1 is a phase change material, liposome nanoparticles having a phase change point at about 42 ℃ can be prepared.
(2) The liposome nanoparticle prepared in example 1 was photographed using transmission electron microscopy.
The results are shown in FIG. 2: the liposome nanoparticle prepared in example 1 had a particle size of about 80nm, and was uniformly distributed and dispersed.
(3) The liposome nanoparticles prepared in example 1 were tested using a malvern particle sizer.
The results are shown in FIG. 3: the liposome nanoparticle prepared in example 1 had a hydrated particle size of about 124nm and a potential of about-26 mV.
Example 3 photothermal treatment of tissue penetration and imaging sensitivity test
The in vitro photoacoustic imaging experimental test method comprises the following steps: the drug PLDD was synthesized according to the preparation method of example 1 so that the final contained photosensitizer DTTB had a concentration of 2.5ug/mL, 5ug/mL, 10ug/mL, 25ug/mL, 50ug/mL, 100ug/mL, and was subjected to photoacoustic signal detection.
The in vivo photoacoustic imaging experimental test method comprises the following steps: the drug PLDD was synthesized according to the preparation method of example 1 so that the final concentration of the photosensitizer DTTB contained was 1mg/mL, and the control group was free photosensitizer DTTB, the concentration of which was 1mg/mL. 100uL of the two medicines are injected into a tumor-bearing mouse body through tail vein, and the tumors are subjected to photoacoustic imaging at 0h, 6h, 12h, 24h and 36h respectively.
The test results are shown in fig. 4-7. PLDD is acronym for each component of the synthetic liposome nanoparticle, representing the liposome nanoparticle synthesized in example 1, DTTB is the near infrared two-region photosensitizer used.
Fig. 4 and 5 show the photoacoustic signals of liposome nanoparticles with different concentrations in vitro and the quantification results thereof, and as can be seen from fig. 4 and 5, the photoacoustic signals of liposome nanoparticles prepared in example 1 increased with increasing concentrations, and the synthesized liposome nanoparticles had excellent photoacoustic signals.
Fig. 6 and fig. 7 are quantitative results of in vivo photoacoustic imaging experiments and photoacoustic signal graphs thereof, and it can be seen from the results that the liposome nanoparticle synthesized in example 1 can detect more obvious photoacoustic signals in tumor body relative to the free photosensitizer DTTB, and the photosensitizer DTTB in the liposome nanoparticle is more easily enriched at the tumor site relative to the free photosensitizer DTTB, so that damage of photothermal treatment to normal tissues adjacent to tumor tissues can be reduced. Therefore, the nano particles can be used for precise imaging guidance, and the enrichment of the visual medicine at the tumor part is guided to determine precise time for administration, so that the problems of deep irradiation and inaccurate irradiation of photothermal treatment are solved.
Example 4 release of DMXAA in liposome nanoparticles
The experimental method comprises the following steps: two 1mL portions of 100ug/mL PLDD were synthesized as in example 1, one portion was irradiated with light at 808nm laser and a power density of 1w/cm 2 The illumination time was 5 minutes. And ultrafiltering two PLDD medicines for 5min under 100kD and 3000rcf, collecting their respective filtrates, and measuring the content of DMXAA by HPLC to obtain released DMXAA content.
The results are shown in fig. 8-10: the synthesized liposome nano-particles can respond to temperature to release the medicine DMXAA, and can play a role of combining with the photosensitizer DTTB to resist tumors. In fig. 8, a chromatogram of DMXAA released from liposome nanoparticles before and after irradiation with light, which was detected using a high performance liquid phase, shows that DMXAA is entrapped in the nanoparticles when no irradiation with light was performed, and thus DMXAA is released due to thermal phase change of the liposome upon irradiation with laser light. Fig. 9 and 10 are electron microscopy images of liposome nanoparticles before and after illumination, respectively, showing that the drug was released after illumination, and smaller and uniform liposome nanoparticles were formed after cooling.
EXAMPLE 5 cytotoxicity of Liposome nanoparticles
The experimental method comprises the following steps: after tumor cells LLC are grown for 24 hours in an adherence way, the medicines in each group are respectively treated according to the concentration of DTTB containing the photosensitizer20ug/mL, 25ug/mL, 30ug/mL, 35ug/mL, 40ug/mL, 45ug/mL are added into the culture medium, and incubated for 4 hours under the condition of cell culture, the illumination group is illuminated under the conditions of 808nm laser and power density of 1w/cm 2 The illumination time is 5 minutes, and the culture is continued for 24 hours under the cell culture condition, and the cells are treated by a CCK8 kit, a live dying kit and an apoptosis kit respectively, and the condition of the cells is detected on the machine.
The results are shown in FIGS. 11-13: the liposome nano-particles synthesized by the invention can improve the incompleteness of photothermal treatment and exert better treatment effect in combination with STING immune channel. Wherein PBS is a control group, laser is a light-only group, PLDT is a liposome nanoparticle group prepared by the method of example 1 and only coated with photosensitizer without dmXAA, PLDD is a liposome nanoparticle group prepared by the method of example 1 and coated with photosensitizer and DXMAA, PLDT (L+) and PLDD (L+) are respectively light-illuminated in the two groups.
FIG. 11 shows the cytotoxicity CCK-8 results of drugs, i.e., the number of viable cells detected by CCK8 kit after treatment of cells with different drug groups; FIG. 12 shows the live and dead staining of cells, i.e., after treatment of cells with different drug groups (40 ug/mL concentration of DTTB containing photosensitizer), live and dead cells were stained with CalceinAM/PI live and dead staining kit, and live and dead fluorescent pictures of cells were obtained by laser confocal imaging; FIG. 13 shows the results of flow-through apoptosis of cells, i.e., cells were stained with Annexin VFITC/PI apoptosis kit after treatment with different drug groups (40 ug/mL concentration of photosensitizer DTTB), and the apoptosis of cells was detected by flow meter for fluorescence. The results of all three experiments showed: the liposome nanoparticle PLDD prepared by the invention has the best cell killing capability in comparison with a PBS control group or a single photo-thermal treatment group, which proves that the liposome nanoparticle constructed by the invention has better killing effect on cancer cells.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (5)
1. The liposome nanoparticle is characterized by being prepared from raw materials including a photosensitizer, a STING signal pathway agonist, a thermal phase change material and a lipid material;
the photosensitizer is a near infrared two-region photosensitizer;
the thermal phase change material is characterized by comprising the following components in percentage by mass: 1 and stearic acid;
the lipid material is prepared from the following components in percentage by mass of 2.5-3.5:1 and distearoyl phosphatidylethanolamine-polyethylene glycol;
the structural formula of the photosensitizer is as follows:
the STING signal pathway agonist is 2, 5-hexanone theobromine;
the mass ratio of the photosensitizer to the STING signal path agonist to the thermal phase change material to the lipid material is 1:1:19-21:24-26.
2. The liposome nanoparticle of claim 1, wherein the lipid material is present in a mass ratio of 3:1 and distearoyl phosphatidylethanolamine-polyethylene glycol.
3. A method of preparing a liposome nanoparticle according to any one of claims 1-2, comprising the steps of:
(1) Dissolving the thermal phase change material in a solvent to obtain a solution of the thermal phase change material;
(2) Dissolving the lipid material in a solvent to obtain a liposome solution;
(3) Respectively dissolving the photosensitizer and the STING signal pathway agonist in a solvent to respectively obtain a photosensitizer solution and a STING signal pathway agonist solution;
(4) And mixing the solution of the thermal phase change material, the photosensitizer solution and the STING signal path agonist solution, dripping the mixture into the preheated liposome solution, performing ultrasonic treatment, and then placing the obtained mixed solution into ice water.
4. A method of preparing liposome nanoparticles according to claim 3, wherein the solvent of step (1) is tetrahydrofuran; and/or the number of the groups of groups,
the concentration of the thermal phase change material in the solution of the thermal phase change material is 3mg/mL-5mg/mL; and/or the number of the groups of groups,
the solvent in the step (2) is 3-5% ethanol water solution; and/or the number of the groups of groups,
the concentration of the lipid material in the liposome solution is 0.5mg/mL-1.5mg/mL; and/or the number of the groups of groups,
the solvent in the step (3) is tetrahydrofuran; and/or the number of the groups of groups,
the concentrations of the photosensitizer solution and the STING signal pathway agonist solution are 2mg/mL-3mg/mL; and/or the number of the groups of groups,
the temperature of the preheated liposome solution is 45-55 ℃; and/or the number of the groups of groups,
the conditions of the ultrasound include: the frequency is 35-45KHZ, the time is 3-8 min, and the temperature is 20-35 ℃.
5. Use of the liposome nanoparticle of any one of claims 1-2 in the preparation of an antitumor drug.
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