A targeted nanomaterial with both photodynamic and chemotherapeutic effects, its preparation method and application

Abstract

The present invention discloses a targeted nanomaterial having both photodynamic and chemical therapeutic effects, and a preparation method and application thereof. The preparation method comprises the following steps: a first stirring reaction is performed on free TCPP [tetra (carboxyphenyl) porphine] and cisplatin in a mixed system of an organic solution and water, and a TCPP nanosphere loaded with cisplatin is obtained after a first separation and purification; a second stirring reaction is performed on the TCPP nanosphere loaded with cisplatin and a tumor targeting peptide in a buffer system, and an external tumor targeting peptide and a TCPP nanosphere loaded with cisplatin are obtained after a second separation and purification. The TCPP ball-cisplatin-polypeptide of the present invention can give full play to the synergistic effect of the three materials, significantly reduce the toxic and side effects during the treatment process, and improve the tumor treatment effect.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and in particular to a targeted nanomaterial having both photodynamic and chemical therapeutic effects, and a preparation method and application thereof. Background Art

[0002] Cancer has become one of the most serious global health problems, and cancer prevention and treatment are urgent. The characteristics of tumor cells such as continuous proliferation, escape from growth inhibition and resistance to cell death determine that malignant tumors are extremely difficult to treat.

[0003] At present, the methods for treating cancer include radiotherapy, chemotherapy, phototherapy, immunotherapy and gene therapy. Cisplatin, with the molecular formula of Cl2(NH3)2Pt, is a commonly used chemotherapy drug for the clinical treatment of malignant tumors. Its main target is intracellular DNA, which can block DNA replication and transcription, produce DNA changes and increase the oxidation level of cells, thereby achieving the effect of killing tumor cells. However, cisplatin is limited in its application due to its non-targeted nature, large toxic side effects and drug resistance. Photodynamic therapy (PDT) has the advantages of low toxicity and repeatable treatment. The three elements of photodynamic therapy are light, photosensitizer and reactive oxygen species. It kills tumor cells by generating ROS through a series of reactions under light irradiation. An ideal photosensitizer is the key to the success of photodynamic therapy. Porphyrin molecules are a class of organic heterocyclic molecules with unique structures, unique chemical and photophysical properties, and have important application value in clinical photodynamic therapy and tumor imaging. However, the poor solubility of porphyrin molecules themselves and their difficulty in enriching in lesions have always been the difficulties that need to be overcome in the field of photodynamic therapy.

[0004] It can be seen that the therapeutic effect of single tumor therapy is limited, and there is an urgent need to provide a new drug to reduce the toxic and side effects during treatment and improve the tumor treatment effect. Summary of the invention

[0005] The purpose of the present invention is to overcome the above technical deficiencies, propose a targeted nanomaterial with both photodynamic and chemotherapeutic effects and a preparation method and application thereof, and solve the technical problem of limited therapeutic effect of single tumor therapy in the prior art.

[0006] In a first aspect, the present invention provides a method for preparing a targeted nanomaterial having both photodynamic and chemotherapeutic effects, comprising the following steps:

[0007] Free TCPP [meso-tetra(carboxyphenyl)porphine] and cisplatin are subjected to a first stirring reaction in a mixed system of an organic solution and water, and TCPP nanospheres loaded with cisplatin are obtained after a first separation and purification;

[0008] The TCPP nanospheres loaded with cisplatin and the tumor targeting peptide are subjected to a second stirring reaction in a buffer system, and the externally connected tumor targeting peptide and the TCPP nanospheres loaded with cisplatin are obtained after a second separation and purification.

[0009] In a second aspect, the present invention provides a targeted nanomaterial having both photodynamic and chemotherapeutic effects, and the targeted nanomaterial having both photodynamic and chemotherapeutic effects is obtained by the method for preparing the targeted nanomaterial having both photodynamic and chemotherapeutic effects provided in the first aspect of the present invention.

[0010] In a third aspect, the present invention provides an application of a targeted nanomaterial having both photodynamic and chemotherapeutic effects, wherein the targeted nanomaterial having both photodynamic and chemotherapeutic effects is used to prepare drugs used for tumor photodynamic therapy and / or chemotherapy.

[0011] Compared with the prior art, the beneficial effects of the present invention include:

[0012] The present invention uses TCPP nanospheres as carriers to load cisplatin. On the one hand, the high specific surface area of ​​the nanospheres is used to better load cisplatin. On the other hand, the nano-size effect is used to improve the biocompatibility of the material, so that the material has passive targeting. By externally connecting tumor targeting peptides, the material can be targeted and enriched in the tumor site, and photodynamic therapy can be accurately performed at the tumor site, and the release of cisplatin is promoted to achieve the synergistic effect of chemical efficacy and phototherapy. The TCPP sphere-cisplatin-polypeptide of the present invention can give full play to the synergistic effect of the three materials, significantly reduce the toxic and side effects during the treatment process, and improve the tumor treatment effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a SEM image of TCPP nanospheres synthesized in Comparative Example 1 of the present invention;

[0014] Figure 2 is a SEM image of the TCPP nanospheres loaded with cisplatin (TCPP spheres-cisplatin) synthesized in Comparative Example 2 of the present invention;

[0015] Figure 3 It is a SEM image of the external tumor targeting peptide synthesized in Example 1 of the present invention and the TCPP nanosphere loaded with cisplatin (TCPP sphere-cisplatin-polypeptide);

[0016] Figure 4 It is a single drug toxicity test result diagram of the TCPP nanospheres synthesized in Comparative Example 1 of the present invention and the TCPP nanospheres loaded with cisplatin (TCPP spheres-cisplatin) synthesized in Comparative Example 2;

[0017] Figure 5 It is a diagram showing the drug uptake test results of the TCPP nanospheres synthesized in Comparative Example 1 of the present invention and the TCPP nanospheres (TCPP sphere-polypeptide) synthesized in Comparative Example 3 with an external tumor targeting peptide;

[0018] Figure 6 It is a graph showing the results of the extracellular singlet oxygen detection test of free TCPP raw material and TCPP nanospheres synthesized in Comparative Example 1;

[0019] Figure 7 It is a graph showing the results of the intracellular reactive oxygen species detection test of the nanospheres synthesized in Example 1 of the present invention and Comparative Examples 1 to 3 and a blank group;

[0020] Figure 8 It is a graph showing the PDT test results of the nanospheres synthesized in Example 1 and Comparative Examples 1-2 of the present invention and the free TCPP raw material;

[0021] Fig. 9 The graph is a result of thermal imaging test on mice of TCPP nanospheres synthesized in comparative example 1 of the present invention and TCPP nanospheres (TCPP sphere-polypeptide) with external tumor targeting peptides synthesized in comparative example 3; wherein a is comparative example 1 and b is comparative example 3. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0023] In a first aspect, the present invention provides a method for preparing a targeted nanomaterial having both photodynamic and chemotherapeutic effects, comprising the following steps:

[0024] S1, subjecting free TCPP [meso-tetra(carboxyphenyl)porphine] and cisplatin to a first stirring reaction in a mixed system of an organic solution and water, and obtaining TCPP nanospheres loaded with cisplatin after a first separation and purification;

[0025] S2, subjecting the TCPP nanospheres loaded with cisplatin and the tumor targeting peptide to a second stirring reaction in a buffer system, and obtaining the externally connected tumor targeting peptide and the TCPP nanospheres loaded with cisplatin after a second separation and purification.

[0026] The present invention self-assembles TCPP into nanospheres, which is not only conducive to loading cisplatin, but also enables it to have passive targeting by integrating the physical and chemical properties of porphyrin with the nano-size effect, thus well solving the problem of poor self-solubility and difficulty in enrichment in lesions, enhancing the photodynamic therapy effect of porphyrin, and promoting the release of cisplatin at the tumor site; the TCPP nanospheres loaded with cisplatin are further connected with tumor targeting peptides, which is conducive to the active targeting and enrichment of TCPP and cisplatin at the tumor site, thereby realizing the combined treatment of photodynamic therapy and chemical drugs.

[0027] In this embodiment, the molar ratio of free TCPP to cisplatin is 1:(0.1-10), including but not limited to 1:0.1, 1:0.2, 1:0.5, 1:1, 1:2, 1:5, 1:10, etc., which is not limited to the present invention.

[0028] In this embodiment, the usage ratio of free TCPP to organic solvent is 1 mg: (0.1-10) ml, including but not limited to 1 mg: 0.1 ml, 1 mg: 0.2 ml, 1 mg: 0.5 ml, 1 mg: 1 ml, 1 mg: 2 ml, 1 mg: 5 ml, 1 mg: 10 ml, etc., which is not limited to the present invention.

[0029] In this embodiment, the usage ratio of free TCPP to water is 1 mg: (10-50) ml, including but not limited to 1 mg: 10 ml, 1 mg: 20 ml, 1 mg: 30 ml, 1 mg: 40 ml, 1 mg: 50 ml, etc., and the present invention is not limited to this.

[0030] In this embodiment, the organic solvent is tetrahydrofuran (THF).

[0031] In this embodiment, the process of performing a first stirring reaction of free TCPP and cisplatin in a mixed system of an organic solution and water is as follows: dissolving free TCPP in an organic solution, then adding cisplatin and water, and performing a first stirring reaction.

[0032] In this embodiment, the first separation and purification process is: extracting the first stirring reaction product by suction filtration, washing with water, and drying, wherein the drying method is vacuum drying, and the drying temperature is room temperature.

[0033] In this embodiment, the tumor targeting peptide is RGD tumor targeting peptide. RGD tumor targeting peptide is a five-membered cyclic peptide composed of arginine, glycine, aspartic acid, D-phenylalanine, and lysine, referred to as c(RGDfK), which can specifically recognize integrin αvβ3 overexpressed in tumor cells.

[0034] In this embodiment, the mass ratio of TCPP to tumor targeting peptide in the TCPP nanosphere loaded with cisplatin is 1: (1-5), including but not limited to 1: 1, 1: 1.5, 1: 2, 1: 2.5, 1: 3, 1: 3.5, 1: 4, 1: 4.5, 1: 5, etc., and the present invention is not limited thereto. Too high a ratio of tumor targeting peptide will affect the light absorption of the material, while too low a ratio will have no targeting effect. Controlling the mass ratio of the two within the ratio range of the present invention has a better effect.

[0035] In this embodiment, the buffer system also contains 0.5-15 mg / ml EDC [1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride)] and 0.1-5 mg / ml NHS (N-hydroxysuccinimide). The addition of EDC and NHS in the present invention is more conducive to the successful externalization of the tumor targeting peptide onto the TCPP ball.

[0036] In this embodiment, the process of performing a second stirring reaction of the TCPP nanospheres loaded with cisplatin and the tumor targeting peptide in a buffer system is as follows:

[0037] S21, adding the TCPP nanospheres loaded with cisplatin into a first buffer solution containing EDC and NHS, and stirring evenly to obtain a first mixed solution;

[0038] S22, dissolving the tumor targeting peptide in a second buffer to obtain a second mixed solution;

[0039] S23, adding the second mixed solution dropwise into the first mixed solution to perform a second stirring reaction.

[0040] The first buffer and the second buffer are PBS buffers. Furthermore, the pH of the PBS buffer is 7.2 to 7.4.

[0041] Among them, in the first mixed solution, the concentration of TCPP nanospheres loaded with cisplatin is 0.1-10 mg / ml, including but not limited to 0.1 mg / ml, 0.5 mg / ml, 1 mg / ml, 2 mg / ml, 5 mg / ml, and 10 mg / ml, which is not limited to the present invention; the concentration of EDC is 1-5 mg / ml, including but not limited to 1 mg / ml, 2 mg / ml, 3 mg / ml, 4 mg / ml, and 5 mg / ml, which is not limited to the present invention; the concentration of NHS is 0.5-3 mg / ml, including but not limited to 0.5 mg / ml, 1 mg / ml, 2 mg / ml, and 3 mg / ml, which is not limited to the present invention.

[0042] Wherein, in the second mixed solution, the concentration of the tumor targeting peptide is 10-50 mg / ml, including but not limited to 10 mg / ml, 20 mg / ml, 30 mg / ml, 40 mg / ml, 50 mg / ml, and the present invention is not limited to this.

[0043] In this embodiment, the second separation and purification process is: transferring the second stirred reaction product to a dialysis bag for pure water dialysis, extraction by suction filtration, water washing, and drying. Further, the molecular weight cutoff of the dialysis bag is 1000-3000Kd, further 2000Kd; the dialysis time is more than 24 hours, further 36 hours; the drying method is vacuum drying, and the drying temperature is room temperature.

[0044] In this embodiment, the temperatures of the first stirring reaction and the second stirring reaction are both room temperature (10-40° C.), and the time of the first stirring reaction and the second stirring reaction are both more than 12 hours, and further 24 hours.

[0045] In a second aspect, the present invention provides a targeted nanomaterial having both photodynamic and chemotherapeutic effects, and the targeted nanomaterial having both photodynamic and chemotherapeutic effects is obtained by the method for preparing the targeted nanomaterial having both photodynamic and chemotherapeutic effects provided in the first aspect of the present invention.

[0046] In a third aspect, the present invention provides an application of a targeted nanomaterial having both photodynamic and chemotherapeutic effects, wherein the targeted nanomaterial having both photodynamic and chemotherapeutic effects is used to prepare drugs used for tumor photodynamic therapy and / or chemotherapy.

[0047] Example 1

[0048] (1) Dissolve 10 mg of free TCPP [meta-tetra(carboxyphenyl)porphine] in 10 ml of THF (tetrahydrofuran), add 3.8 mg of cisplatin and 250 ml of pure water, stir in a water bath at room temperature for 24 h, extract by suction, wash twice with pure water, and dry in a vacuum at 25° C. to obtain TCPP nanospheres loaded with cisplatin (TCPP spheres-cisplatin).

[0049] (2) Add cisplatin-loaded TCPP nanospheres (quantified at 5 mg TCPP, i.e., dissolve cisplatin-loaded TCPP nanospheres in PBS and quantify according to the standard curve of ultraviolet absorption value) to a mixed solution prepared by 4.6 mg EDC, 3.5 mg NHS and 3 ml PBS (pH 7.2-7.4), stir at room temperature for 1 hour, dissolve 12.5 mg RGD [Cyclo (RGDfk)] in 500 ul PBS (pH 7.2-7.4), add dropwise to the reaction system, and continue stirring for 24 hours. Transfer to a 2000Kd dialysis bag for pure water dialysis for 36 hours, extract by suction, wash twice with pure water, and vacuum dry at 25°C to obtain TCPP nanospheres loaded with external tumor targeting peptide and cisplatin (TCPP sphere-cisplatin-peptide).

[0050] Comparative Example 1

[0051] Dissolve 10 mg of free TCPP [meta-tetra(carboxyphenyl)porphine] in 10 ml of THF, add 250 ml of pure water, stir in a water bath at room temperature for 24 h, extract by suction, wash twice with pure water, and dry in a vacuum at 25° C. to obtain self-assembled TCPP nanospheres.

[0052] Comparative Example 2

[0053] Dissolve 10 mg of free TCPP [meta-tetra(carboxyphenyl)porphine] in 10 ml of THF, add 3.8 mg of cisplatin and 250 ml of pure water, stir in a water bath at room temperature for 24 hours, extract by suction, wash twice with pure water, and dry in a vacuum at 25°C to obtain TCPP nanospheres loaded with cisplatin (TCPP spheres-cisplatin).

[0054] Comparative Example 3

[0055] (1) Dissolve 10 mg of free TCPP [meta-tetra(carboxyphenyl)porphine] in 10 ml of THF, add 250 ml of pure water, stir in a water bath at room temperature for 24 h, extract by suction, wash twice with pure water, and dry in a vacuum at 25° C. to obtain self-assembled TCPP nanospheres.

[0056] (2) Add 5 mg of TCPP nanospheres to a mixed solution prepared by 4.6 mg of EDC, 3.5 mg of NHS and 3 ml of PBS (pH 7.2-7.4), stir at room temperature for 1 h, dissolve 12.5 mg of RGD [Cyclo (RGDfk)] in 500 ul of PBS (pH 7.2-7.4), add dropwise to the reaction system, and continue stirring for 24 h. Transfer to a 2000 Kd dialysis bag for pure water dialysis for 36 h, extract by suction, wash twice with pure water, and vacuum dry at 25 ° C to obtain TCPP nanospheres with external tumor targeting peptides (TCPP sphere-peptide).

[0057] pass Figures 1 to 3 It can be seen that Example 1 of the present invention successfully synthesized TCPP nanospheres (TCPP sphere-cisplatin-polypeptide) with external tumor targeting peptide and loaded with cisplatin.

[0058] Experimental Group

[0059] Cellular toxicity

[0060] 4T1 cells were evenly seeded in a 96-well plate, with approximately 10,000 cells per well, and cultured in a constant temperature incubator (37°C, 5% CO2) for 24 hours. The supernatant was removed, and different nanomaterials were configured with 1640 culture medium into a concentration gradient of 0, 2, 5, 10, 20, 40, and 100 ug / ml. 0.1 ml was added to each well, and the culture was continued in the constant temperature incubator for 4 hours. Then 10 ul of serum was added to each well, and the plates were cultured at a constant temperature for 24 hours for MTT detection.

[0061] pass Figure 4It can be seen that within the concentration range of 100ug / ml, both nano-drug delivery systems have no obvious cytotoxicity, and compared with simple TCPP spheres, the cisplatin-loaded TCPP nanospheres have lower cytotoxicity when the concentration is greater than 40ug / ml, indicating that the cisplatin-loaded TCPP nanospheres synthesized in the present invention can exert the synergistic effect of cisplatin and TCPP nanospheres and reduce the toxicity of high-concentration drugs.

[0062] Drug intake

[0063] 4T1 cells were evenly inoculated in a 24-well plate, with about 60,000 cells in each well. The plates were cultured in a constant temperature incubator (37°C, 5% CO2) for 24 hours. The supernatant was removed and different nanomaterials were configured into concentration gradients of 5 and 10 ug / ml using 1640 culture medium. 0.6 ml was added to each well. After 4 hours of culture in the constant temperature incubator, 100 ul of trypsin was added to each well for digestion. The culture was terminated with 200 ul of 1640 culture medium containing serum and the plates were transferred to centrifuge tubes for detection by flow cytometry.

[0064] pass Figure 5 It can be seen that TCPP nanospheres with external tumor targeting peptides are more easily taken up by cells.

[0065] Extracellular singlet oxygen detection

[0066] The nanomaterial was added to 0.1 mg / ml DPBF (diphenylisobenzofuran) and mixed to make the final concentration of the nanomaterial 10 ug / ml. 2 The maximum absorption value was detected at 415 nm after irradiation for 45, 112 and 180 s respectively under the same conditions.

[0067] pass Figure 6 It can be seen that both free TCPP and TCPP nanospheres can produce singlet oxygen under light conditions, but TCPP nanospheres have a better ability to produce reactive oxygen species.

[0068] Intracellular reactive oxygen species detection

[0069] 4T1 cells were evenly seeded in a 24-well plate, with about 60,000 cells per well. The plates were cultured in a constant temperature incubator (37°C, 5% CO2) for 24 hours. The supernatant was removed and different nanomaterials were prepared into a concentration of 10ug / ml using 1640 culture medium. 0.6ml was added to each well. After culturing in a constant temperature incubator for 3.5 hours, 400ul of pre-diluted (1:250) DCFH-DA probe was added to each well to make the final concentration of 10uM. The plates were then cultured in a constant temperature incubator for 0.5 hours. The concentration of the probes was 400ul and the final concentration was 10uM. 2 The cells were trypsinized and then illuminated for 0, 45 and 112 s, and reactive oxygen species were detected by flow cytometry.

[0070] pass Figure 7 It can be seen that the TCPP nanospheres with external tumor targeting peptides and loaded with cisplatin (TCPP spheres-cisplatin-peptide) have the strongest ability to produce reactive oxygen and are significantly better than other nanomaterials, indicating that the combination of cisplatin, tumor targeting peptides and TCPP nanospheres can exert a synergistic effect of the three and significantly improve the ability of the resulting TCPP spheres-cisplatin-peptide to produce reactive oxygen.

[0071] PDT testing

[0072] 4T1 cells were evenly seeded in a 96-well plate, with about 10,000 cells per well. The plates were cultured in a constant temperature incubator (37°C, 5% CO2) for 24 hours. The supernatant was removed and different nanomaterials were prepared into a concentration of 10ug / ml using 1640 culture medium. 0.1ml was added to each well and the plates were cultured in a constant temperature incubator for 4 hours. The nanomaterials were then illuminated with a wavelength of 660nm, 80mW / cm 2 The cells were illuminated for 45, 112 and 180 seconds respectively, 10 μl of serum was added to each well, and the cells were cultured at a constant temperature for 24 hours for MTT assay.

[0073] pass Figure 8 It can be seen that the TCPP nanosphere material with external tumor targeting peptide and cisplatin loaded (TCPP sphere-cisplatin-peptide) effectively exerts the synergistic effect of photodynamic therapy and chemotherapy. It has a good effect of killing tumor cells under light, and due to its targeting effect, it can be well enriched in the tumor site, which is expected to achieve tumor treatment.

[0074] In vivo thermal imaging of mice

[0075] BALB / c male mice were inoculated with 10 6 4T1 cells were inoculated one week later and 200ul of nanomaterials were injected into the tail vein at 5mg / kg. Thermal imaging was performed at 1, 2, 3, 4, 5, 6, and 7h.

[0076] pass Fig. 9 It can be seen that the TCPP nanospheres with external tumor targeting peptides are targeted and enriched in the tumor site, which can well achieve targeted drug transport, and further illustrate that the TCPP sphere-cisplatin-polypeptide synthesized by the present invention also has good targeting.

[0077] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for preparing a targeted nanomaterial having both photodynamic and chemical therapeutic effects, characterized in that: The following steps are involved: The free TCPP and cisplatin are subjected to a first stirring reaction in a mixed system of an organic solvent and water, and the cisplatin-loaded TCPP nanospheres are obtained after a first separation and purification; The TCPP nanospheres loaded with cisplatin and the tumor targeting peptide are subjected to a second stirring reaction in a buffer system, and the external tumor targeting peptide and the TCPP nanospheres loaded with cisplatin are obtained after a second separation and purification; wherein, The tumor targeting peptide is RGD tumor targeting peptide.

2. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The molar ratio of free TCPP to cisplatin is 1:(0.1-10); the mass ratio of TCPP to tumor targeting peptide in the cisplatin-loaded TCPP nanospheres is 1:(1-5).

3. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The usage ratio of the free TCPP to the organic solvent is 1 mg: (0.1-10) ml; the usage ratio of the free TCPP to water is 1 mg: (10-50) ml.

4. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The organic solvent is tetrahydrofuran.

5. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The process of performing a first stirring reaction of free TCPP and cisplatin in a mixed system of an organic solvent and water is as follows: dissolving free TCPP in an organic solvent, then adding cisplatin and water, and performing a first stirring reaction; the process of performing a second stirring reaction of the cisplatin-loaded TCPP nanospheres and the tumor targeting peptide in a buffer system is as follows: adding the cisplatin-loaded TCPP nanospheres to a first buffer solution containing EDC and NHS, stirring evenly, to obtain a first mixed solution; and dissolving the tumor targeting peptide in a second buffer solution, to obtain a second mixed solution; The second mixed solution is added dropwise to the first mixed solution to perform a second stirring reaction.

6. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 5, characterized in that: The first buffer and the second buffer are PBS buffer; in the first mixed solution, the concentration of the TCPP nanospheres loaded with cisplatin is 0.1-10 mg / ml, the concentration of the EDC is 1-5 mg / ml, and the concentration of the NHS is 0.5-3 mg / ml; in the second mixed solution, the concentration of the tumor targeting peptide is 10-50 mg / ml.

7. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The temperatures of the first stirring reaction and the second stirring reaction are both room temperature, and the times of the first stirring reaction and the second stirring reaction are both more than 12 hours.

8. The method for preparing the targeted nanomaterial having both photodynamic and chemical therapeutic effects according to claim 1, characterized in that: The first separation and purification process is: extracting the first stirring reaction product by suction filtration, washing with water, and drying; The second separation and purification process is: transferring the second stirred reaction product to a dialysis bag for pure water dialysis, suction filtration extraction, water washing, and drying.

9. A targeted nanomaterial with both photodynamic and chemotherapeutic effects, characterized in that: The targeted nanomaterial having both photodynamic and chemotherapeutic effects is obtained by the method for preparing the targeted nanomaterial having both photodynamic and chemotherapeutic effects as claimed in any one of claims 1 to 8.

10. An application of the targeted nanomaterial having both photodynamic and chemical therapeutic effects as claimed in claim 9, characterized in that: The targeted nanomaterial having both photodynamic and chemical therapeutic effects is used to prepare medicines used in tumor photodynamic therapy and / or chemotherapy.

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