Drug delivery system for resisting tumors through combination of Tianfo ginseng active substance and photodynamic therapy

Abstract

The invention relates to the technical field of biological medicine and tumor treatment, in particular to an anti-tumor drug delivery system combining a Tianfo ginseng active substance with a photodynamic therapy, which is characterized in that a composite active extract is prepared by extracting and purifying traditional Chinese medicine components, and the composite active extract and a photosensitizer are jointly loaded in a liposome nano-carrier modified by polypeptide. According to the system, targeted delivery and retention of drugs at tumor parts are achieved by optimizing the structural design, the anti-tumor effect is synergistically enhanced in combination with the photodynamic therapy, and the treatment accuracy and curative effect are remarkably improved. The invention also provides a preparation method and an application mode of the system, the system is suitable for treating various solid tumors, has the characteristics of high efficiency and low toxicity, and provides a new path for the development of antitumor drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine and tumor treatment, and specifically is a drug delivery system for anti-tumor combining Tianfoshen active substance with photodynamic therapy. Background Art

[0002] With the deepening of research into anti-tumor effects of traditional Chinese medicine, drug delivery systems based on active ingredients from natural medicines have gradually become a research hotspot in the field of cancer treatment. In particular, formulations based on traditional Chinese medicine combinations such as American ginseng, toad venom, asparagus cochinchinensis, fritillaria thunbergii, Acanthopanax obovata, kiwi fruit root, sea buckthorn fruit, and bergamot have shown promising application prospects due to their multi-target mechanisms of action and low toxicity and side effects. However, existing technologies still have shortcomings in drug delivery system design, preparation processes, and combined applications with other therapeutic approaches (such as photodynamic therapy), limiting further improvement in their clinical efficacy. Patent publication number CN108135894B discloses a tumor therapeutic agent for combination therapy with lenvatinib, ifosfamide, and etoposide. This patent achieves anti-tumor effects through the combination of multiple compounds, but it primarily focuses on the development of Western medicine compounds and does not address the application of traditional Chinese medicine active ingredients or the design of synergistic enhancement with modern therapeutic approaches (such as photodynamic therapy). Furthermore, the drug delivery system used in this approach is relatively traditional and lacks design for precise delivery to the tumor site, which may affect drug distribution and targeting in the body. A search revealed that patent publication number WO2018041261A1 discloses a tumor therapeutic drug derived from erythrocyte vesicles. This patent utilizes vesicles released by apoptotic erythrocytes as carriers to encapsulate therapeutic drugs, enhancing their stability and safety in vivo. However, this technical solution primarily focuses on the construction of vesicle carriers and drug encapsulation, without explicitly mentioning the introduction of active ingredients from traditional Chinese medicines. Furthermore, the patent fails to integrate the design with modern physical treatments such as photodynamic therapy, potentially limiting its potential for multimodal anti-tumor therapy.

[0003] The above problems indicate that the existing technology still needs to be improved in terms of the design of drug delivery systems for active substances in traditional Chinese medicine, the improvement of targeting, and the synergistic application with photodynamic therapy. Therefore, the present invention provides a drug delivery system for the anti-tumor effect of Tianfoshen active substance combined with photodynamic therapy. The purpose is to improve the targeting and retention of drugs at the tumor site by optimizing the structure and function of the drug delivery system, and at the same time, combine with the synergistic effect of photodynamic therapy to significantly enhance the anti-tumor effect, thus meeting the clinical demand for efficient and precise anti-tumor treatment. Summary of the Invention

[0004] The present invention provides a drug delivery system for the anti-tumor effect of Tianfoshen active substances combined with photodynamic therapy, which aims to improve the targeting and retention ability of drugs at the tumor site by optimizing the structure and function of the drug delivery system, and at the same time combine the synergistic effect of photodynamic therapy to significantly enhance the anti-tumor effect and meet the clinical demand for efficient and precise anti-tumor treatment.

[0005] In a first aspect, the present invention provides a method for preparing a Tianfoshen active substance combined with a photodynamic therapy anti-tumor drug delivery system, comprising the following steps: S10: extracting and purifying American ginseng, toad venom, asparagus cochinchinensis, fritillaria thunbergii, Acanthopanax obovata, kiwi fruit root, sea buckthorn fruit, and bergamot respectively to obtain active extracts of the Chinese medicinal ingredients; S20: mixing the above active extracts in a mass ratio of 1 to 5:1 to 3:1 to 4:1 to 2:1 to 3:1 to 5:1 to 2:1 to 4 to obtain a composite active extract; S30: preparing a tumor-targeting nanocarrier, wherein the nanocarrier is composed of a liposome modified with a polypeptide; S40: loading the composite active extract into the nanocarrier to form drug-loaded nanoparticles; S50: introducing a photosensitizer into the drug-loaded nanoparticles to form a combined drug delivery system; S60: Surface modification of the combined drug delivery system enhances its stability in the body's circulation and tumor targeting. According to the present invention, liposomes are used as the core material of the nanocarrier due to their excellent biocompatibility and drug encapsulation capabilities, effectively protecting the active extract from the complex in vivo environment. Tumor targeting is imparted to the nanocarrier through peptide modification. This peptide is a short-chain RGD-sequence peptide that specifically recognizes the integrin αvβ3 on tumor neovascularization, thereby achieving selective aggregation at the tumor site.

[0006] In some embodiments, in step S10, the extraction process utilizes ultrasonic-assisted extraction, with the extraction solvent being an aqueous ethanol solution with a volume fraction of 50% to 80% ethanol, the extraction temperature being 40°C to 60°C, the ultrasonic frequency being 20 kHz to 40 kHz, and the ultrasonic duration being 20 to 60 minutes. After extraction, purification is performed using a macroporous adsorption resin to remove impurities and enrich the active ingredient.

[0007] In some embodiments, in step S30, the liposomes are composed of phospholipids and cholesterol in a mass ratio of 3 to 5:1 to 2, the phospholipids include soy lecithin or hydrogenated lecithin, and the cholesterol is food-grade cholesterol. The liposomes are prepared using a thin film dispersion method, which specifically comprises dissolving the phospholipids and cholesterol in an organic solvent, evaporating the organic solvent to form a uniform thin film, then adding a buffer solution for hydration, adjusting the pH to 6.5 to 7.5, and finally performing probe sonication to obtain liposomes with a particle size of 100 nm to 200 nm.

[0008] In some embodiments, in step S30, peptide modification is performed using a chemical coupling method, first activating the carboxyl groups on the liposome surface, which then react with the amino groups of the peptide to form an amide bond. The activation process uses N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as catalysts, with a reaction temperature of 4°C to 25°C and a reaction time of 2 to 6 hours.

[0009] In some embodiments, in step S40, the composite active extract is loaded into the liposomes by passive diffusion, with the loading amount being 10% to 30% of the total mass of the liposomes. To improve the loading efficiency, an appropriate amount of glycerol or polyethylene glycol can be added as a stabilizer during the hydration process, at a concentration of 1% to 5%.

[0010] In some embodiments, in step S50, the photosensitizer is a porphyrin compound or a phthalocyanine compound, preferably 5-aminolevulinic acid (ALA) or zinc phthalocyanine (ZnPc). The photosensitizer is immobilized on the surface of the drug-loaded nanoparticles via covalent bonding or physical adsorption, with the immobilized amount being 5% to 15% of the total mass of the drug-loaded nanoparticles.

[0011] In some embodiments, in step S60, the surface is modified with polyethylene glycol (PEG) molecules with a molecular weight of 2,000 to 5,000. The PEG molecules are attached to the surface of the drug-loaded nanoparticles via chemical coupling. The coupling process involves the reaction of maleimide groups with sulfhydryl groups to form thioether bonds. The reaction temperature is 4°C to 25°C, and the reaction time is 4 to 12 hours. The modified combined drug delivery system exhibits prolonged in vivo circulation and significantly increased accumulation at the tumor site.

[0012] In the second aspect, the present invention provides a drug delivery system for the anti-tumor effect of Tianfoshen active substance combined with photodynamic therapy, which is prepared according to the method described in any embodiment of the first aspect. According to the present invention, the combined drug delivery system realizes the co-delivery of the composite active extract and the photosensitizer through the design of the nanocarrier, and can achieve high-concentration drug distribution at the tumor site. The photosensitizer produces singlet oxygen under the irradiation of a light source of a specific wavelength, inducing tumor cell apoptosis. At the same time, the composite active extract exerts a multi-target mechanism of action, inhibiting tumor cell proliferation and regulating the immune microenvironment. In some embodiments, the combined drug delivery system exhibits excellent anti-tumor effects in in vivo experiments. After administration through tail vein injection, the accumulation amount of the combined drug delivery system at the tumor site is 3 to 5 times that of unmodified nanoparticles, and the tumor growth inhibition rate reaches 70% to 90%. In addition, the combined drug delivery system has low toxicity to normal tissues, and no obvious liver and kidney function damage was observed.

[0013] In some embodiments, the combined drug delivery system can be applied to a variety of solid tumor types, including breast cancer, lung cancer, gastric cancer, and colorectal cancer. For different tumor types, the surface modification strategy of the nanocarrier can be adjusted according to the characteristics of the tumor microenvironment, such as introducing other targeting ligands or polysaccharide molecules to further improve targeting.

[0014] In a third aspect, the present invention provides a method for applying a combined drug delivery system in photodynamic therapy, comprising the following steps: A10: administering the combined drug delivery system by intravenous injection at a dose of 5 mg to 20 mg per kilogram of body weight; A20: irradiating the tumor site with a laser having a wavelength of 630 nm to 690 nm within 24 to 48 hours after administration, with a light intensity of 50 mW / cm² to 150 mW / cm² and an irradiation time of 10 minutes to 30 minutes; A30: monitoring changes in tumor volume and hematological indicators to evaluate therapeutic efficacy and safety. According to the present invention, the application of the combined drug delivery system in photodynamic therapy achieves the optimal match between drug release and photosensitizer activation by precisely controlling the administration time and illumination time. Under illumination conditions, the singlet oxygen generated by the photosensitizer not only directly kills tumor cells, but also enhances the penetration ability of the composite active extract, further improving the therapeutic effect.

[0015] In some embodiments, in step A20, the laser light source is a continuous wave laser with an adjustable output power range of 100 mW to 500 mW. The wavelength is adjusted based on the absorption characteristics of the photosensitizer. To avoid local overheating, intermittent cooling can be performed during the irradiation process, with a cooling time of 5 to 10 seconds.

[0016] In some embodiments, in step A30, changes in tumor volume are monitored by ultrasound imaging or magnetic resonance imaging, and hematological indicators include white blood cell count, platelet count, and liver and kidney function indicators. The monitoring frequency is once a week for 4 to 6 weeks. In a fourth aspect, the present invention provides the use of a combined drug delivery system in the preparation of an anti-tumor drug.

[0017] According to the present invention, the combined drug delivery system overcomes the shortcomings of existing technologies in the design of drug delivery systems for active substances in traditional Chinese medicine, improved targeting, and synergistic application with photodynamic therapy by optimizing the drug delivery structure and functional design, demonstrating significant technical advantages and clinical application potential.

[0018] In some embodiments, the combined drug delivery system can be prepared into a powder formulation through a freeze-drying process for long-term storage and transportation. Freeze-drying conditions include pre-freezing at -40°C to -60°C for 12 to 24 hours, then warming to -20°C to 0°C under vacuum conditions and holding for 6 to 12 hours, and then warming to 20°C to 30°C and holding for 2 to 4 hours. Reconstitution is performed using physiological saline or glucose injection, with the reconstitution volume being 80% to 120% of the original volume.

[0019] In some embodiments, the quality control method of the combined drug delivery system includes particle size distribution measurement, Zeta potential measurement, and encapsulation efficiency measurement. Particle size distribution is measured using dynamic light scattering, with a particle size range of 100 nm to 200 nm; Zeta potential is measured using electrophoretic light scattering, with a Zeta potential range of -20 mV to -40 mV; and encapsulation efficiency is measured using ultrafiltration centrifugation, with an encapsulation efficiency range of 70% to 90%. In summary, the present invention significantly improves the targeting and efficacy of traditional Chinese medicine active substances in tumor treatment by optimizing the design and preparation process of the drug delivery system and combining it with the synergistic effect of photodynamic therapy, providing a new technical path for the development of efficient and precise anti-tumor drugs. DETAILED DESCRIPTION

[0020] In this specification, each embodiment or implementation scheme is described in a progressive manner, and each embodiment focuses on the differences from other embodiments. In the description of this specification, the reference terms "one embodiment", "some embodiments", "illustrative embodiments", "example", "specific example", or "some examples" are intended to refer to specific features, structures, materials or characteristics described in conjunction with the implementation or example that are included in at least one implementation or example of the present application. In this specification, the schematic representation of the above terms does not necessarily refer to the same implementation or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more implementations or examples in a suitable scheme.

[0021] In a first aspect, the present application provides a method for preparing a Tianfoshen active substance combined with a photodynamic therapy anti-tumor drug delivery system, comprising the following steps: S10: extracting and purifying American ginseng, toad venom, asparagus cochinchinensis, fritillaria thunbergii, Acanthopanax obovata, kiwi fruit root, sea buckthorn fruit, and bergamot respectively to obtain active extracts of the Chinese medicinal ingredients; S20: mixing the above active extracts in a mass ratio of 1 to 5:1 to 3:1 to 4:1 to 2:1 to 3:1 to 5:1 to 2:1 to 4 to obtain a composite active extract; S30: preparing a tumor-targeting nanocarrier, wherein the nanocarrier is composed of a liposome modified with a polypeptide; S40: loading the composite active extract into the nanocarrier to form drug-loaded nanoparticles; S50: introducing a photosensitizer into the drug-loaded nanoparticles to form a combined drug delivery system; S60: Surface modification of the combined drug delivery system to increase its stability in the body's circulation and its targeting to the tumor site.

[0022] According to the present application, in step S10, the extraction process uses ultrasonic-assisted extraction, the extraction solvent is an ethanol-water solution, wherein the ethanol volume fraction is 50% to 80%, the extraction temperature is 40°C to 60°C, the ultrasonic frequency is 20kHz to 40kHz, and the ultrasonic time is 20 minutes to 60 minutes. After the extraction is completed, a macroporous adsorption resin is used for purification to remove impurities and enrich the active ingredients.

[0023] In some embodiments, in step S10, the extraction solvent is a mixture of ethanol and water in a volume ratio of 1:1 to 4:1. During the extraction process, ultrasound-assisted extraction can significantly improve the extraction efficiency of the active ingredient while reducing the loss of heat-sensitive components. After extraction, purification is performed using a macroporous adsorption resin such as D101 or AB-8. The active ingredient is further enriched by adjusting the concentration and flow rate of the eluent. The eluent is an ethanol-water solution with an ethanol volume fraction of 30% to 70% and a flow rate of 1 mL / min to 5 mL / min.

[0024] In some embodiments, the mass ratio of the active extracts in step S20 can be adjusted based on the specific tumor type. For example, in breast cancer treatment, the mass ratio of American ginseng to Acanthopanax obovata can be set at 3:2, while in lung cancer treatment, the mass ratio of Fritillaria thunbergii to Actinidia chinensis root can be set at 4:1. During the mixing process, a stirrer is used at a speed of 200 to 500 rpm for 10 to 30 minutes to ensure uniform mixing.

[0025] In some embodiments, in step S30, the liposomes are composed of phospholipids and cholesterol in a mass ratio of 3 to 5:1 to 2, the phospholipids include soy lecithin or hydrogenated lecithin, and the cholesterol is food-grade cholesterol. The liposomes are prepared using a thin film dispersion method, which specifically comprises dissolving the phospholipids and cholesterol in an organic solvent, evaporating the organic solvent to form a uniform thin film, then adding a buffer solution for hydration, adjusting the pH to 6.5 to 7.5, and finally performing probe sonication to obtain liposomes with a particle size of 100 nm to 200 nm.

[0026] In some embodiments, in step S30, peptide modification utilizes chemical coupling, first activating the carboxyl groups on the liposome surface, which then react with the amino groups of the peptide to form an amide bond. The activation process uses N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as catalysts, with a reaction temperature of 4°C to 25°C and a reaction time of 2 to 6 hours. The peptide is a short-chain peptide with an RGD sequence, and its concentration is 0.5 mg / mL to 2 mg / mL.

[0027] In some embodiments, in step S40, the composite active extract is loaded into the liposomes by passive diffusion, with the loading amount ranging from 10% to 30% of the total liposome mass. To improve loading efficiency, an appropriate amount of glycerol or polyethylene glycol can be added as a stabilizer during the hydration process at a concentration of 1% to 5%. After loading, the encapsulation efficiency is measured using ultrafiltration centrifugation, and the encapsulation efficiency ranges from 70% to 90%.

[0028] In some embodiments, in step S50, the photosensitizer is a porphyrin or phthalocyanine compound, preferably 5-aminolevulinic acid (ALA) or zinc phthalocyanine (ZnPc). The photosensitizer is immobilized on the surface of the drug-loaded nanoparticles via covalent bonding or physical adsorption, with the immobilized amount ranging from 5% to 15% of the total mass of the drug-loaded nanoparticles. During the immobilization process, the pH is adjusted to 6.0 to 7.0 using a buffer solution. The particle size distribution is measured by dynamic light scattering, and the particle size range is 100 nm to 200 nm.

[0029] In some embodiments, in step S60, the surface is modified with polyethylene glycol (PEG) molecules with a molecular weight of 2,000 to 5,000. The PEG molecules are attached to the surface of the drug-loaded nanoparticles via chemical coupling. The coupling process involves the reaction of maleimide groups with sulfhydryl groups to form thioether bonds. The reaction temperature is 4°C to 25°C, and the reaction time is 4 to 12 hours. The modified combined drug delivery system exhibits prolonged in vivo circulation and significantly increased accumulation at the tumor site.

[0030] In a second aspect, the present application provides a drug delivery system for anti-tumor effects of a combination of a Tianfoshen active substance and photodynamic therapy, which is prepared according to the method of any embodiment of the first aspect.

[0031] In some embodiments, the combined drug delivery system can be prepared into a powder formulation through a freeze-drying process for long-term storage and transportation. Freeze-drying conditions include pre-freezing at -40°C to -60°C for 12 to 24 hours, then warming to -20°C to 0°C under vacuum conditions and holding for 6 to 12 hours, and then warming to 20°C to 30°C and holding for 2 to 4 hours. Reconstitution is performed using physiological saline or glucose injection, with the reconstitution volume being 80% to 120% of the original volume.

[0032] In some embodiments, quality control methods for the combined drug delivery system include particle size distribution measurement, zeta potential measurement, and encapsulation efficiency measurement. Particle size distribution is measured using dynamic light scattering, with a particle size range of 100 nm to 200 nm; zeta potential is measured using electrophoretic light scattering, with a zeta potential range of -20 mV to -40 mV; and encapsulation efficiency is measured using ultrafiltration centrifugation, with an encapsulation efficiency range of 70% to 90%.

[0033] On the third aspect, the present application provides an application method of a combined drug delivery system in photodynamic therapy, comprising the following steps: A10: administering the combined drug delivery system by intravenous injection at a dose of 5 mg to 20 mg per kilogram of body weight; A20: within 24 to 48 hours after administration, using a laser with a wavelength of 630 nm to 690 nm to irradiate the tumor site, with a light intensity of 50 mW / cm² to 150 mW / cm², and an irradiation time of 10 minutes to 30 minutes; A30: monitoring changes in tumor volume and hematological indicators to evaluate the treatment effect and safety.

[0034] In some embodiments, in step A20, the laser light source is a continuous wave laser with an adjustable output power range of 100 mW to 500 mW. The wavelength is adjusted based on the absorption characteristics of the photosensitizer. To avoid local overheating, intermittent cooling can be performed during the irradiation process, with a cooling time of 5 to 10 seconds.

[0035] In some embodiments, in step A30, changes in tumor volume are monitored by ultrasound imaging or magnetic resonance imaging, and hematological indicators include white blood cell count, platelet count, and liver and kidney function indicators. The monitoring frequency is once a week for 4 to 6 weeks. The following describes an embodiment of the present application.

[0036] The examples described below are exemplary and are intended only to explain the present invention and are not to be construed as limiting the present invention. Where specific techniques or conditions are not specified in the examples, the methods or conditions described in the literature within the art or in the product specifications were used. Where the manufacturer of the reagents or instruments is not specified, all are commercially available conventional products. Example

[0037] Preparation of combined drug delivery system: S10: American ginseng, toad venom, asparagus cochinchinensis, Fritillaria thunbergii, Acanthopanax obovata, kiwi fruit root, sea buckthorn fruit, and bergamot were ground and subjected to ultrasonic-assisted extraction using 70% ethanol-water solution at 50°C, 30 kHz, and 40 minutes. After extraction, the extracts were purified using D101 macroporous adsorption resin, with the eluent being 50% ethanol-water solution at a flow rate of 3 mL / min.

[0038] S20: The above active extracts were mixed in a mass ratio of 3:2:4:1:2:3:1:2, and stirred with a stirrer at a rotation speed of 300 rpm for 20 minutes to obtain a composite active extract.

[0039] S30: Soy lecithin and food-grade cholesterol were dissolved in chloroform at a mass ratio of 4:1. The chloroform was evaporated to form a thin film, which was then hydrated by adding phosphate buffer solution. The pH was adjusted to 7.0, and liposomes with a particle size of 150 nm were obtained by probe sonication.

[0040] S40: The composite active extract was loaded into liposomes at a loading amount of 20% of the total mass of the liposomes, and polyethylene glycol at a concentration of 3% was added as a stabilizer during the hydration process.

[0041] S50: Zinc phthalocyanine was used as a photosensitizer and fixed on the surface of drug-loaded nanoparticles by physical adsorption, with the fixed amount being 10% of the total mass of the drug-loaded nanoparticles.

[0042] S60: A PEG molecule with a molecular weight of 3000 was used to modify the surface of the combined drug delivery system. During the coupling process, the maleimide group reacted with the sulfhydryl group to form a thioether bond. The reaction temperature was 10°C and the reaction time was 8 hours.

[0043] Example 2 Application of combined drug delivery system: A10: The combined drug delivery system prepared in Example 1 was administered via tail vein injection at a dose of 10 mg per kilogram of body weight.

[0044] A20: 36 hours after administration, the tumor site was irradiated with a laser of 650nm wavelength, with a light intensity of 100mW / cm² and an irradiation time of 20 minutes.

[0045] A30: Monitor tumor volume changes through ultrasound imaging, and detect white blood cell count, platelet count, and liver and kidney function indicators through hematological indicators. The monitoring frequency is once a week and the monitoring is continued for 5 weeks. Example 3 Freeze-drying process of combined drug delivery system: The combined drug delivery system prepared in Example 1 was pre-frozen at -50°C for 18 hours, then heated to -10°C under vacuum and held for 10 hours, and then heated to 25°C and held for 3 hours to obtain a lyophilized powder. Reconstitution with physiological saline was performed, and the reconstitution volume was 100% of the original volume.

[0046] Comparative Example 1 Preparation of a combined drug delivery system without polypeptide modification: Steps S10 to S50 are the same as those in Example 1, except that no surface modification with PEG molecules is performed in step S60.

[0047] Comparative Example 2 Preparation of a photosensitizer-free combined drug delivery system: Steps S10 to S40 are the same as in Example 1, except that no photosensitizer is introduced in step S50. **Experimental Data Comparison** The combined drug delivery systems prepared in the above examples and comparative examples were applied to a solid tumor model, and tumor volume changes and hematological indicators were recorded. The results are shown in the following table: .

[0048] Experimental data show that the combined drug delivery systems of Examples 1 to 3 significantly outperformed Comparative Examples 1 and 2 in terms of tumor volume reduction, while also exhibiting low toxicity to normal tissues, with no significant liver or kidney damage observed. The lack of surface modification in Comparative Example 1 resulted in reduced accumulation at the tumor site and a reduced therapeutic effect. The lack of a photosensitizer in Comparative Example 2 prevented the synergistic effects of photodynamic therapy, further weakening the therapeutic effect.

Claims

1. A method for preparing a Tianfoshen active substance combined with photodynamic therapy anti-tumor drug delivery system, characterized in that: The following steps are involved: S10: extracting and purifying American ginseng, toad venom, asparagus cochinchinensis, fritillaria thunbergii, Acanthopanax obovata, kiwi fruit root, sea buckthorn fruit, and bergamot respectively to obtain active extracts of the Chinese medicinal ingredients; S20: mixing the above active extracts in a mass ratio of 1 to 5:1 to 3:1 to 4:1 to 2:1 to 3:1 to 5:1 to 2:1 to 4 to obtain a composite active extract; S30: preparing a tumor-targeting nanocarrier, wherein the nanocarrier is composed of a liposome modified with a polypeptide; S40: loading the composite active extract into the nanocarrier to form drug-loaded nanoparticles; S50: introducing a photosensitizer into the drug-loaded nanoparticles to form a combined drug delivery system; S60: Surface modification of the combined drug delivery system to increase its stability in the body's circulation and its targeting to the tumor site.

2. The method according to claim 1, characterized in that In step S10, the extraction process adopts ultrasonic-assisted extraction, the extraction solvent is ethanol aqueous solution, wherein the ethanol volume fraction is 50% to 80%, the extraction temperature is 40°C to 60°C, the ultrasonic frequency is 20kHz to 40kHz, and the ultrasonic time is 20 minutes to 60 minutes.

3. The method according to claim 1, characterized in that In step S30, the liposomes are composed of phospholipids and cholesterol in a mass ratio of 3 to 5:1 to 2, the phospholipids include soybean lecithin or hydrogenated lecithin, and the cholesterol is food-grade cholesterol.

4. The method according to claim 3, characterized in that In step S30, the preparation method of liposomes adopts the thin film dispersion method, which specifically comprises the following steps: dissolving phospholipids and cholesterol in an organic solvent, evaporating the organic solvent to form a uniform thin film, adding a buffer solution for hydration, adjusting the pH value to 6.5 to 7.5, and finally obtaining liposomes with a particle size of 100 nm to 200 nm by probe ultrasonic treatment.

5. The method according to claim 1, wherein In step S30, the polypeptide is modified by chemical coupling. The carboxyl groups on the surface of the liposomes are first activated and then reacted with the amino groups of the polypeptide to form an amide bond. N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are used as catalysts during the activation process. The reaction temperature is 4°C to 25°C and the reaction time is 2 hours to 6 hours.

6. The method according to claim 1, characterized in that In step S40, the composite active extract is loaded into the liposome by passive diffusion, and the loading amount is 10% to 30% of the total mass of the liposome.

7. The method according to claim 1, characterized in that In step S50, the photosensitizer is a porphyrin compound or a phthalocyanine compound, and the photosensitizer is fixed on the surface of the drug-loaded nanoparticles by covalent bonding or physical adsorption, and the fixed amount is 5% to 15% of the total mass of the drug-loaded nanoparticles.

8. The method according to claim 1, characterized in that In step S60, the surface is modified using polyethylene glycol molecules with a molecular weight of 2000 to 5000; the polyethylene glycol molecules are connected to the surface of the drug-loaded nanoparticles by chemical coupling. During the coupling process, maleimide groups react with sulfhydryl groups to form thioether bonds. The reaction temperature is 4°C to 25°C, and the reaction time is 4 hours to 12 hours.

9. A drug delivery system for anti-tumor combined with Tianfoshen active substance and photodynamic therapy, characterized in that: Prepared according to the method according to any one of claims 1 to 8.

10. A method for using a Tianfoshen active substance combined with a photodynamic therapy anti-tumor drug delivery system in photodynamic therapy, characterized in that: The method includes the following steps: A10: Administer the combined drug delivery system by intravenous injection at a dose of 5 mg to 20 mg per kilogram of body weight; A20: Within 24 to 48 hours after administration, irradiate the tumor site with a laser with a wavelength of 630 nm to 690 nm, with a light intensity of 50 mW / cm² to 150 mW / cm² and an irradiation time of 10 to 30 minutes; A30: Monitor changes in tumor volume and hematological indicators to evaluate treatment efficacy and safety.

11. An application of a Tianfoshen active substance combined with a photodynamic therapy anti-tumor drug delivery system in the preparation of an anti-tumor drug, characterized in that: The drug delivery system is prepared into a powder preparation through a freeze-drying process, and the freeze-drying conditions are pre-freezing at -40°C to -60°C for 12 to 24 hours, then heating to -20°C to 0°C under vacuum conditions and maintaining for 6 to 12 hours, and then heating to 20°C to 30°C and maintaining for 2 to 4 hours.