A porphyrin-based oxygen-carrying polymer sonosensitizer, a preparation method and application thereof

Abstract

The present application relates to the technical field of nanobiomedicine, and particularly relates to a porphyrin oxygen-carrying polymer sonosensitizer, a preparation method and application thereof; the porphyrin oxygen-carrying polymer sonosensitizer takes porphyrin as a main body structure and takes polyheptafluorobutyramide as a polymer side chain. The polyheptafluorobutyramide contained in the porphyrin oxygen-carrying polymer sonosensitizer can carry oxygen, and under the activation of ultrasound, the perfluoroalkyl-modified polymer can release oxygen explosively, the perfluoroalkyl-modified polymer triggered by visible light increases oxygen supply to relieve tumor hypoxia, reverses a low-oxygen microenvironment, enhances the generation of reactive oxygen species in the SDT process, further improves the accumulation efficiency at a tumor site, improves the effect of SDT in treating tumors, and becomes an effective method for enhancing the chemical sonodynamic therapy of hypoxic tumors.

Description

Technical Field

[0001] This invention relates to the field of nanobiomedical technology, and in particular to a porphyrin-based oxygen-carrying polymer sound-sensing agent, its preparation method, and its application. Background Technology

[0002] Currently, while traditional cancer treatments such as chemotherapy, radiotherapy, and surgery play a role to some extent, their drawbacks are significant. Chemotherapy drugs, while killing cancer cells, damage normal cells, causing a series of serious side effects such as nausea, vomiting, hair loss, and weakened immunity, greatly impacting patients' quality of life. Radiotherapy, when used for local treatment, causes radiation damage to surrounding normal tissues, and long-term effects may lead to tissue fibrosis and functional impairment. Surgical treatment is highly invasive, with long recovery times, and for some advanced or metastatic cancers, surgery is often insufficient to completely remove cancer cells, easily leading to recurrence and metastasis. Therefore, there is an urgent need to find safer and more effective cancer treatment methods.

[0003] Sonodynamic therapy (SDT), as a novel cancer treatment method, has received widespread attention in recent years. It achieves localized destruction of tumor tissue through the interaction of sound waves and nanomaterials, offering advantages such as targeted delivery, minimal invasiveness, and reusability. Compared to traditional cancer treatments, SDT not only directly kills tumor cells but also stimulates the body's immune response, enhancing anti-tumor immune function. This improves treatment efficacy while reducing harm and side effects to the body.

[0004] Organic sonosensitizers are a key component of SDT (Sonochemical Therapy). Activated by ultrasonic irradiation, they generate ROS (reactive oxygen species) via sonoluminescence or sonochemical pyrolysis, thereby exerting a killing effect on tumor cells. Typically, photosensitizers can be used as sonosensitizers. The molecular design of sonosensitizers is often derived from photosensitizers, mainly classified into four categories: porphyrin derivatives, anthocyanin derivatives, other small-molecule sonosensitizers, and semiconductor polymers. Compared to inorganic nanomaterials, organic sonosensitizers exhibit high biocompatibility, excellent biodegradability, significant tumor targeting and accumulation potential, and are readily metabolized from the liver or kidneys in live mice, demonstrating strong potential for biomedical applications.

[0005] Porphyrins and their derivatives, due to their excellent photosensitizing activity, are widely used as first-generation photosensitizers in photodynamic therapy and have also been extensively studied in the field of sonodynamic therapy. Common porphyrin-derived sonosensitizers include protoporphyrin (IX), hematoporphyrin (HP), hematoporphyrin monomethyl ether (HP), dihydroporphyrin e6 (Ce6), Ce6-C15-ethyl ester, verteporfen, temoporfen, sodium median porphyrin (DVDMS), 5-aminolevulinic acid (5-ALA), and phthalocyanine-artesunate conjugates. These sonosensitizers have similar 18-carbon aromatic macrocyclic carbon core structures and can generate reactive oxygen species (ROS) under ultrasound irradiation. However, they generally have some problems, such as poor water solubility, which leads to poor dispersion in the physiological environment and affects their effect on tumor tissue; high biosafety issues, which may pose potential harm to normal tissues; and low tumor-targeting accumulation capacity, which makes it difficult to accumulate efficiently at the tumor site, limiting the effect of sonodynamic therapy and greatly hindering their widespread application in SDT. Summary of the Invention

[0006] The purpose of this invention is to provide a porphyrin-based oxygen-carrying polymer sonic sensitizer, its preparation method, and its application, so as to overcome the shortcomings of existing porphyrin-derived sonic sensitizers in SDT applications and improve the efficacy of tumor treatment.

[0007] To achieve the above objectives, this invention provides a porphyrin-based oxygen-carrying polymer sound-sensing agent, with porphyrin as the main structure and polyheptafluorobutyramide as the polymeric side chain, as shown in the following structural formula.

[0008]

[0009] In the formula, m is the degree of polymerization, where m = 40 to 60.

[0010] The porphyrin-based oxygen-carrying polymer sonosensitive agent of this invention has a porphyrin main structure that can provide sonodynamic effects; it contains polymeric side chains for modifying oxygen-carrying perfluorinated compounds to enhance sonodynamic effects. Specifically, heptafluorobutyramide on the side chains is covalently linked to the polymer side end, forming polyheptafluorobutyramide capable of carrying oxygen. Under ultrasonic activation conditions, the polymer containing perfluoroalkyl groups undergoes a change, achieving an explosive release of oxygen. This process helps enhance the efficacy of sonodynamic therapy for tumors. When triggered by visible light, it can increase oxygen supply, alleviate tumor hypoxia, reverse the hypoxic microenvironment, enhance ROS generation during SDT, improve the accumulation efficiency at the tumor site, and improve the efficacy of SDT for tumor treatment.

[0011] This invention also provides a method for preparing the above-mentioned porphyrin-based oxygen-carrying polymer sound-sensing agent, comprising the following steps:

[0012] S1. Under light-protected conditions, porphyrin monomers, triethylamine, and 2-bromoisobutyryl bromide were mixed with a solvent and reacted under nitrogen protection to prepare molecule 1.

[0013] S2. In a light-protected environment, molecule 1 and N-succinimide acrylate were mixed with a solvent, and then a catalyst was added. Under nitrogen protection, N,N,N',N”,N”-pentamethyldiethylenetriamine was added to carry out an atom transfer radical polymerization reaction to prepare polymer 1.

[0014] S3. Under light-protected conditions, polymer 1 and heptafluorobutyramide are added to a solvent, and triethylamine is added under nitrogen protection to carry out an amidation reaction to prepare polymer 2, namely porphyrin-based oxygen-carrying polymer sound-sensing agent.

[0015] Preferably, the molar ratio of porphyrin monomer, triethylamine and 2-bromoisobutyryl bromide in S1 is 1:8:15.

[0016] Preferably, the solvent in S1 is dichloromethane, the reaction temperature is 25°C, and the reaction time is 48h.

[0017] Preferably, the molar ratio of molecule 1 and N-succinimide acrylate in S2 is 1:50 to 200.

[0018] Preferably, the solvent in S2 is anisole and the catalyst is cuprous bromide.

[0019] Preferably, the reaction temperature of the atom transfer radical polymerization reaction in S2 is 80-100℃, and the reaction time is 9-12h.

[0020] Preferably, the molar ratio of polymer 1 to heptafluorobutyramide in S3 is 1:1.2.

[0021] Preferably, the solvent in S3 is N,N-dimethylformamide, the reaction temperature of the amidation reaction is 35-60℃, and the reaction time is 24-60h.

[0022] The present invention also provides the application of the above-mentioned porphyrin-based oxygen-carrying polymer sonosensitive agent in a targeted sonosensitive agent complex for sonodynamic therapy.

[0023] The beneficial effects of this invention are:

[0024] (1) The porphyrin-based oxygen-carrying polymer acoustic sensitizer of the present invention has a porphyrin main structure to provide acoustic dynamic effect, contains polymer side chains to modify oxygen-carrying perfluorinated compounds to improve acoustic dynamic effect, and heptafluorobutyramide on the side chain is covalently connected to the side end of the polymer. The polyheptafluorobutyramide contained therein can not only carry oxygen, but also release oxygen explosively under the activation of ultrasound. The perfluorinated polymer triggered by visible light increases oxygen supply to alleviate tumor hypoxia, reverses the hypoxic microenvironment, enhances the generation of reactive oxygen species during SDT, further improves the accumulation efficiency of tumor sites, and improves the effect of SDT in treating tumors.

[0025] (2) The preparation method of the porphyrin-based oxygen-carrying polymer sound-sensing agent of the present invention has clear steps, mild reaction conditions, is easy to operate and control, and is suitable for large-scale preparation;

[0026] (3) The porphyrin-based oxygen-carrying polymer sonosensitive agent of the present invention has the advantages of improving tumor target enrichment, relieving hypoxia and increasing oxygen supply when used in SDT to treat tumors, and is expected to become an effective method to enhance the chemosonodynamic therapy of hypoxic tumors.

[0027] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0028] Figure 1 The absorption spectrum of molecule 1 prepared in Example 1 of this invention;

[0029] Figure 2 The absorption spectrum of polymer 2 prepared in Example 1 of this invention is shown.

[0030] Figure 3 The above is the hydrogen nuclear magnetic resonance spectrum of molecule 1 obtained in Example 1 of this invention;

[0031] Figure 4 The above is the 1H NMR spectrum of polymer 1 obtained in Example 1 of this invention;

[0032] Figure 5 The hydrogen nuclear magnetic resonance spectrum of polymer 2 obtained in Example 1 of this invention;

[0033] Figure 6 The fluorine spectrum of polymer 2 obtained in Example 1 of this invention;

[0034] Figure 7 This is an oxygen-carrying diagram of polymer 2 obtained in Example 1 of the present invention;

[0035] Figure 8 The image shows the acoustic dynamics of the reference molecule DPBF in this invention.

[0036] Figure 9 The image shows the acoustic dynamics of polymer 2 obtained in Example 1 of this invention.

[0037] Figure 10 The image shows the acoustic dynamics of the polymer 2 prepared in Example 1 of this invention after being loaded with oxygen.

[0038] Figure 11 This is a cell survival rate graph showing the cytotoxicity of the targeted porphyrin-based oxygen-carrying small molecule sonosensitive agent prepared in Example 1 of this invention on mouse breast cancer cells. Detailed Implementation

[0039] The present invention will be further described below with reference to the accompanying drawings and embodiments. Unless otherwise defined, the technical or scientific terms used in this invention should be understood in their ordinary sense by those skilled in the art. The features mentioned above or in the specific examples mentioned in this invention can be combined arbitrarily, and these specific embodiments are only used to illustrate the invention and are not intended to limit the scope of the invention.

[0040] This invention provides a porphyrin-based oxygen-carrying polymer sound-sensing agent, with porphyrin as the main structure and polyheptafluorobutyramide as the polymeric side chain. The specific structural formula is as follows.

[0041]

[0042] In the formula, m is the degree of polymerization, where m = 40 to 60.

[0043] This invention also provides a method for preparing the above-mentioned porphyrin-based oxygen-carrying polymer sound-sensing agent, comprising the following steps:

[0044] S1. Under light-protected conditions, porphyrin monomers, triethylamine, and 2-bromoisobutyryl bromide were mixed with a solvent and reacted under nitrogen protection to prepare molecule 1.

[0045] S2. In a light-protected environment, molecule 1 and N-succinimide acrylate were mixed with a solvent, and then a catalyst was added. Under nitrogen protection, N,N,N',N”,N”-pentamethyldiethylenetriamine was added to carry out an atom transfer radical polymerization reaction to prepare polymer 1.

[0046] S3. Under light-protected conditions, polymer 1 and heptafluorobutyramide are added to a solvent, and triethylamine is added under nitrogen protection to carry out an amidation reaction to prepare polymer 2, namely porphyrin-based oxygen-carrying polymer sound-sensing agent.

[0047] In some embodiments of the present invention, the specific structural formula of molecule 1 in S1 is as follows.

[0048]

[0049] In some embodiments of the present invention, the polymer 1 in S2 has the following specific structural formula.

[0050]

[0051] Preferably, the molar ratio of porphyrin monomer, triethylamine and 2-bromoisobutyryl bromide in S1 is 1:8:15.

[0052] In some embodiments of the present invention, the porphyrin monomer in S1 is 5,10,15,20-tetra(4-hydroxyphenyl)-2H,24H-porphyrin.

[0053] In some embodiments of the present invention, in step S1, porphyrin monomers are first added to a solvent and completely dissolved, then vacuumed, and then triethylamine is added. After stirring at room temperature for 30 minutes, 2-bromoisobutyryl bromide is added.

[0054] Preferably, the solvent in S1 is dichloromethane, the reaction temperature is 25°C, and the reaction time is 48h.

[0055] In some embodiments of the present invention, the amount of dichloromethane used in S1 is 20 mL.

[0056] In some embodiments of the present invention, the reaction process of S1 is as follows:

[0057]

[0058] In some embodiments of the present invention, after reaction S1 is completed, the reaction is quenched with water, extracted with dichloromethane, and the product is evaporated to dryness before purification by column chromatography to obtain molecule 1. The present invention does not limit the developing solvent used for purification; any solvent well-known to those skilled in the art may be used.

[0059] Preferably, the molar ratio of molecule 1 and N-succinimide acrylate in S2 is 1:50 to 200.

[0060] In some embodiments of the present invention, the molar ratio of molecule 1 to N-succinimide acrylate is 1:60.

[0061] In some embodiments of the present invention, the reaction process of S2 is as follows:

[0062]

[0063] Preferably, the solvent in S2 is anisole and the catalyst is cuprous bromide.

[0064] Preferably, the reaction temperature of the atom transfer radical polymerization reaction in S2 is 80-100℃, and the reaction time is 9-12h.

[0065] In some embodiments of the present invention, the reaction temperature of the atom transfer radical polymerization reaction in S2 is 90°C and the reaction time is 12h.

[0066] In some embodiments of the present invention, after the S2 reaction is completed, the product is filtered through an organic filter membrane and then repeatedly precipitated in diethyl ether to obtain polymer 1. The present invention does not limit the number of precipitation cycles; any method well-known to those skilled in the art can be used.

[0067] Preferably, the molar ratio of polymer 1 to heptafluorobutyramide in S3 is 1:1.2.

[0068] In some embodiments of the present invention, the reaction process of S3 is as follows:

[0069]

[0070] Preferably, the solvent in S3 is N,N-dimethylformamide (DMF), the reaction temperature of the amidation reaction is 35-60℃, and the reaction time is 24-60h.

[0071] In some embodiments of the present invention, the reaction temperature of the amidation reaction in S3 is 50°C and the reaction time is 48h.

[0072] In some embodiments of the present invention, after the S3 reaction is completed, the product is filtered through an organic filter membrane and then repeatedly precipitated in diethyl ether to obtain polymer 2. The present invention does not limit the number of precipitation cycles; any method well-known to those skilled in the art can be used.

[0073] The present invention also provides the application of the above-mentioned porphyrin-based oxygen-carrying polymer sonosensitive agent in a targeted sonosensitive agent complex for sonodynamic therapy.

[0074] Example 1

[0075] This invention provides a method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent, comprising the following steps:

[0076] S1. Under light-protected conditions, the acceptor molecule 5,10,15,20-tetra(4-hydroxyphenyl)-2H,24H-porphyrin (100 mg, 0.1 mM) was dissolved in 20 mL of dichloromethane in a reaction tube. The mixture was then subjected to vacuum treatment, and the donor molecule triethylamine (240 mg, 1.5 mM) was added. After stirring at room temperature for 30 min, the donor molecule 2-bromoisobutyryl bromide (270 mg, 0.8 mM) was added. The reaction was carried out under nitrogen protection at 25 °C for 48 hours. Finally, the reaction was quenched with water, and after extraction with dichloromethane, the product was evaporated to dryness and then purified by column chromatography to obtain molecule 1.

[0077] S2. Under light-protected conditions, molecule 1 (100 mg) and N-succinimide acrylate (796 mg, 5.24 mM) were dissolved in 2 mL of anisole in a reaction tube. Then, CuBr catalyst was added, and N,N,N',N”,N”-pentamethyldiethylenetriamine (200 μL) was added as a ligand under nitrogen protection. The reaction was carried out at 90 °C for 12 h. After the reaction was completed, the solid catalyst was removed by filtration through an organic filter membrane. Then, the product was repeatedly precipitated in diethyl ether to obtain a reddish-brown conjugated main chain polymer with N-succinimide acrylate side chain substitution, polymer 1 (900 mg).

[0078] S3. Under light-protected conditions, polymer 1 (300 mg) and heptafluorobutyramide (1.75 mmol) were dissolved in 5 mL of DMF. Triethylamine (1.75 mmol) was added under nitrogen protection. The mixture was stirred at 50 °C for 48 h. After the reaction was completed, the mixture was filtered through an organic filter membrane to remove the solid catalyst. Then, the mixture was repeatedly precipitated in diethyl ether to prepare polymer 2, which is a porphyrin-based oxygen-carrying polymer sound-sensing agent.

[0079] Example 2

[0080] This invention provides a method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent, comprising the following steps:

[0081] S1. Under light-protected conditions, the acceptor molecule 5,10,15,20-tetra(4-hydroxyphenyl)-2H,24H-porphyrin (100 mg, 0.1 mM) was dissolved in 20 mL of dichloromethane in a reaction tube. The mixture was then subjected to vacuum treatment, and the donor molecule triethylamine (240 mg, 1.5 mM) was added. After stirring at room temperature for 30 min, the donor molecule 2-bromoisobutyryl bromide (270 mg, 0.8 mM) was added. The reaction was carried out under nitrogen protection at 25 °C for 48 hours. Finally, the reaction was quenched with water, and after extraction with dichloromethane, the product was evaporated to dryness and then purified by column chromatography to obtain molecule 1.

[0082] S2. Under light-protected conditions, molecule 1 (100 mg) and N-succinimide acrylate (796 mg, 5.24 mM) were dissolved in 2 mL of anisole in a reaction tube. Then, CuBr catalyst was added, and N,N,N',N”,N”-pentamethyldiethylenetriamine (200 μL) was added as a ligand under nitrogen protection. The reaction was carried out at 80 °C for 12 h. After the reaction was completed, the solid catalyst was removed by filtration through an organic filter membrane. Then, the product was repeatedly precipitated in diethyl ether to obtain a reddish-brown conjugated main chain polymer with N-succinimide acrylate side chain substitution, polymer 1 (900 mg).

[0083] S3. Under light-protected conditions, polymer 1 (300 mg) and heptafluorobutyramide (1.75 mmol) were dissolved in 5 mL of DMF. Triethylamine (1.75 mmol) was added under nitrogen protection. The mixture was stirred at 35 °C for 60 h. After the reaction was completed, the mixture was filtered through an organic filter membrane to remove the solid catalyst. Then, the mixture was repeatedly precipitated in diethyl ether to prepare polymer 2, which is a porphyrin-based oxygen-carrying polymer sound-sensing agent.

[0084] Example 3

[0085] This invention provides a method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent, comprising the following steps:

[0086] S1. Under light-protected conditions, the acceptor molecule 5,10,15,20-tetra(4-hydroxyphenyl)-2H,24H-porphyrin (100 mg, 0.1 mM) was dissolved in 20 mL of dichloromethane in a reaction tube. The mixture was then subjected to vacuum treatment, and the donor molecule triethylamine (240 mg, 1.5 mM) was added. After stirring at room temperature for 30 min, the donor molecule 2-bromoisobutyryl bromide (270 mg, 0.8 mM) was added. The reaction was carried out under nitrogen protection at 25 °C for 48 hours. Finally, the reaction was quenched with water, and after extraction with dichloromethane, the product was evaporated to dryness and then purified by column chromatography to obtain molecule 1.

[0087] S2. Under light-protected conditions, molecule 1 (100 mg) and N-succinimide acrylate (796 mg, 5.24 mM) were dissolved in 2 mL of anisole in a reaction tube. Then, CuBr catalyst was added, and N,N,N',N”,N”-pentamethyldiethylenetriamine (200 μL) was added as a ligand under nitrogen protection. The reaction was carried out at 100 °C for 9 h. After the reaction was completed, the solid catalyst was removed by filtration through an organic filter membrane. Then, the product was repeatedly precipitated in diethyl ether to obtain a reddish-brown conjugated main chain polymer with N-succinimide acrylate side chain substitution, polymer 1 (900 mg).

[0088] S3. Under light-protected conditions, polymer 1 (300 mg) and heptafluorobutyramide (1.75 mmol) were dissolved in 5 mL of DMF. Triethylamine (1.75 mmol) was added under nitrogen protection. The mixture was stirred at 60 °C for 24 h. After the reaction was completed, the mixture was filtered through an organic filter membrane to remove the solid catalyst. Then, the mixture was repeatedly precipitated in diethyl ether to prepare polymer 2, which is a porphyrin-based oxygen-carrying polymer sound-sensing agent.

[0089] Characterization experiments and performance testing

[0090] Using dichloromethane as the organic solvent, organic solutions of molecule 1 and polymer 2 from Example 1 were prepared, and their absorption spectra were tested. Nuclear magnetic resonance (NMR) detection was also performed on molecule 1, polymer 1, and polymer 2 prepared in Example 1, and the results are as follows: Figure 1-5 As shown.

[0091] from Figure 1 The absorption spectrum shows that the absorption peak of molecule 1 is located in the 500 nm band; from Figure 3 The proton NMR spectrum shows the same characteristic proton signal as molecule 1, indicating that molecule 1 was successfully prepared in Example 1.

[0092] from Figure 2 The absorption spectrum shows that the absorption peak of polymer 2 is located in the 550 nm band; from Figure 5The proton NMR spectrum shows the same characteristic proton signal as that of polymer 2, indicating that polymer 2 was successfully prepared in Example 1.

[0093] from Figure 4 The proton NMR spectrum shows the same characteristic proton signal as that of polymer 1, indicating that polymer 1 was successfully prepared in Example 1.

[0094] Fluorine spectrum detection: The polymer 2 prepared in Example 1 was subjected to fluorine spectrum detection to obtain the fluorine spectrum of polymer 2, as shown below. Figure 6 As shown, the corresponding characteristic signals can be seen, indicating that heptafluorobutyramide has been successfully linked to the polymer side via covalent bonds, and its chemical structure has not been significantly damaged during the synthesis process. This ensures the integrity of the polyheptafluorobutyramide function, helps to guarantee the reliability of its oxygen-carrying and oxygen-releasing properties, and thus improves the stability of the therapeutic effect.

[0095] Oxygen loading detection: The oxygen loading of polymer 2 prepared in Example 1 was detected, with water as a control group, to obtain the oxygen loading map of polymer 2, as shown below. Figure 7 As shown, polymer 2 has oxygen-carrying capacity. After being loaded with oxygen, polymer 2 can store and slowly release oxygen, indicating that it has good oxygen-carrying performance and good stability. This shows that the side chain of polyheptafluorobutyramide successfully plays the role of carrying oxygen, providing a material basis for alleviating tumor hypoxia in subsequent sonodynamic therapy, which helps to enhance the production of reactive oxygen species and improve the therapeutic effect.

[0096] Acoustodynamic testing: A saturated solution of the reference molecule DPBF was prepared using ethanol as a solvent, and its acoustic dynamics were tested as a comparison. The results are as follows: Figure 8 As shown; the organic solution of polymer 2 from Example 1 was prepared using a solvent of ethanol:water = 1:1, and the acoustic dynamics were tested. The results are as follows. Figure 9 As shown; similarly, using ethanol:water = 1:1 as a solvent, an organic solution of the oxygen-loaded polymer 2 was prepared and its acoustic dynamics were tested. The results are as follows. Figure 10 As shown.

[0097] By comparison Figures 8-10 It can be seen that different substances (DPBF, polymer 2, polymer 2 + oxygen) have different sonodynamic effects at the same time (5 minutes). DPBF can be used as a reference molecule and serve as a reference standard for sonodynamic effects. Compared with DPBF, polymer 2 has a 7% reduction in sonodynamic effect, showing a significant sonodynamic effect. Polymer 2 + oxygen has a 24% reduction in sonodynamic effect after oxygen loading, showing a more significant sonodynamic effect, which is beneficial to improving the effect of sonodynamic therapy.

[0098] Cytotoxicity test: Polymer 2 from Example 1 was prepared into cell culture media with different concentration gradients (the highest polymer concentration was 2 mg / mL), and cultured with mouse breast cancer cells for 4 hours. CCK-8 reagent was added, and cell viability was calculated by measuring absorbance at 450 nm. The results are as follows: Figure 11 As shown, polymer 2 has very low toxicity to breast cancer cells, indicating that the porphyrin-based oxygen-carrying polymer sonosensitive agent prepared in this invention has good biocompatibility. This makes it less damaging to normal cells when used for tumor treatment, thus improving the safety and feasibility of sonodynamic therapy.

[0099] Therefore, the porphyrin-based oxygen-carrying polymer sonosensitive agent provided by this invention can effectively bind and store oxygen, has good acoustic response characteristics, good biocompatibility and stability, and can enhance the killing effect of sonodynamic therapy on tumor cells, meeting the needs of different tumor treatments, and is expected to become a new and highly effective tumor treatment drug.

[0100] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A porphyrin-based oxygen-carrying polymer sound-sensing agent, characterized in that: With porphyrin as the main structure and polyheptafluorobutyramide as the polymeric side chain, the specific structural formula is as follows. ； In the formula, m is the degree of polymerization, where m = 40~60.

2. A method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent as described in claim 1, characterized in that: Includes the following steps, S1. Under light-protected conditions, porphyrin monomers, triethylamine, and 2-bromoisobutyryl bromide were mixed with a solvent and reacted under nitrogen protection to prepare molecule 1. S2. In a light-protected environment, molecule 1 and N-succinimide acrylate were mixed with a solvent, and then a catalyst was added. Under nitrogen protection, N,N,N',N'',N''-pentamethyldiethylenetriamine was added to carry out an atom transfer radical polymerization reaction to prepare polymer 1. S3. Under light-protected conditions, polymer 1 and heptafluorobutyramide are added to a solvent, and triethylamine is added under nitrogen protection to carry out an amidation reaction to prepare polymer 2, namely porphyrin-based oxygen-carrying polymer sound-sensing agent.

3. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The molar ratio of porphyrin monomers, triethylamine, and 2-bromoisobutyryl bromide in S1 is 1:8:

15.

4. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The solvent in S1 is dichloromethane, the reaction temperature is 25℃, and the reaction time is 48h.

5. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The molar ratio of molecule 1 and N-succinimide acrylate in S2 is 1:50~200.

6. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The solvent in S2 is anisole, and the catalyst is cuprous bromide.

7. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The reaction temperature for the atom transfer radical polymerization reaction in S2 is 80-100℃, and the reaction time is 9-12h.

8. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: In S3, the molar ratio of polymer 1 to heptafluorobutyramide is 1:1.

2.

9. The method for preparing a porphyrin-based oxygen-carrying polymer sound-sensing agent according to claim 2, characterized in that: The solvent in S3 is N,N-dimethylformamide, the reaction temperature of the amidation reaction is 35-60℃, and the reaction time is 24-60h.

10. An application of the porphyrin-based oxygen-carrying polymer sound-sensing agent as described in claim 1, characterized in that: For the preparation of targeted sonosensitive agent complexes for sonodynamic therapy.

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