A preparation method of a type I photosensitizer material based on a polymer aggregation microenvironment regulation, a type I photosensitizer material and applications

Abstract

The application provides a preparation method of a type I photosensitizer material based on polymer aggregation microenvironment regulation, the type I photosensitizer material and application. The preparation method comprises the following steps: dissolving raw materials including a multi-block polymer with a hydrophobic segment and an ionic segment and a photosensitizer in a solvent A, adding dropwise into water under the action of ultrasonic, and obtaining the type I photosensitizer material after post-treatment. The application is based on the polymer aggregation microenvironment regulation concept, establishes a mode of using polymer wrapping to combine with the photosensitizer to realize the construction of the type I photosensitizer, is more simple compared with the prior art, the method has certain universality, and the obtained type I photosensitizer material has excellent performance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of photosensitizer materials, and further relates to a preparation method of a type I photosensitizer material based on polymer aggregation microenvironment regulation, the type I photosensitizer material and application. BACKGROUND

[0002] Cancer has a high mortality rate and has always been a serious threat to people's health. With the progress of science and technology, the means of treating cancer have been improved, and some emerging treatment methods have also emerged. People pursue lower side effects and smaller damage, such as photodynamic therapy, photothermal therapy, immunotherapy, etc. Among them, photodynamic therapy (PDT) has been widely studied and applied. Photodynamic therapy requires the simultaneous presence of light, photosensitizer and oxygen, and the photosensitizer is excited by a specific light source to react with oxygen to produce reactive oxygen species (ROS). The high activity of ROS has biological toxicity to proteins, DNA and lipids, and in addition, ROS can destroy the intracellular redox balance, and under the action of multiple effects, the purpose of killing tumor cells is achieved. PDT has unique advantages in disease treatment, such as small invasiveness, good treatment effect, low biological toxicity, high targeting, etc., and has attracted the attention, research and development of many scholars.

[0003] The photosensitizer reaches the singlet state after being excited by light, and then reaches the triplet state through intersystem crossing. The triplet exciton is easy to react with oxygen to produce ROS. There are mainly two ways to produce ROS in this process. One is that the triplet exciton produces hydroxyl radicals, superoxide anions, hydrogen peroxide and other ROS through electron transfer to oxygen. The second is that the triplet exciton produces singlet oxygen through energy transfer to oxygen. According to the two ways, photosensitizers can be divided into type I and type II photosensitizers. Since the beginning of the 20th century, most of the developed photosensitizers are through the type II energy transfer pathway to produce singlet oxygen, which requires a large amount of oxygen. However, the rapid metabolism of tumor tissue causes anoxic tumor microenvironment, and type II photosensitizers face the problem of insufficient oxygen supply, which limits the treatment effect of PDT. In contrast, type I photosensitizers produce ROS through electron transfer, which can reduce the dependence on oxygen and show great medical value in overcoming the anoxic dilemma in PDT.

[0004] The current type I photosensitizer construction mainly relies on the design and synthesis of molecules, introducing strong donor / acceptor units, heavy atoms, metal atoms, ionic groups, etc. in the molecular structure. Although chemical synthesis can obtain better type I photosensitizer molecules, the method is specific and not suitable for all photosensitizer molecules, lacking universality, such as the modification of traditional photosensitizers DCF TFM, FL, PpIX in Chinese invention patent CN114306624A to improve the performance of photosensitizers, but the photosensitizers involved need to have carboxyl groups; in the published literature (Dye. Pigm. 2021, 194, 109651. Chem. Sci. 2020, 11, 3405-3417), type I photosensitizer construction is achieved by introducing heavy atom effect, but the photosensitizers involved have phenothiazine or phosphine oxide rich electron groups in the structure, which is not suitable for all photosensitizers.

[0005] The existing technology is mainly the structural design and synthesis of photosensitizer molecules, which has complicated synthesis steps, low yield, time-consuming, high cost, and poor universality. Therefore, it is necessary to start from other ideas other than the structure of photosensitizer molecules, and to study a type I photosensitizer construction method with certain universality, which can better broaden the development of photosensitizer materials in PDT treatment and other aspects. SUMMARY

[0006] In order to solve the technical problems existing in the prior art, the present application provides a preparation method of type I photosensitizer material based on polymer aggregation microenvironment regulation, type I photosensitizer material and application.

[0007] The present application proposes a universal type I photosensitizer construction method to solve the problem of lack of universal type I photosensitizer construction method, and the obtained photosensitizer material can be applied to photodynamic therapy, photodynamic antibiosis, photocatalytic pollutant degradation, etc.

[0008] The existing type I photosensitizer construction method is mainly the structural design at the molecular level, but the molecular structure design is complex, the synthesis steps are complicated, the yield is low, the time is long, and the cost is high. The present application prepares a multi-block polymer with hydrophobic and ionic segments, which is combined with traditional photosensitizers by using polymer wrapping to construct nanoparticle type I photosensitizers. The polymer wrapped photosensitizer forms nanoparticles, constructs a polymer aggregation microenvironment around the photosensitizer, and establishes the combination of photosensitizers by using polymer wrapping to realize type I photosensitizer construction.

[0009] The concept in the present application is innovative, and compared with the existing technology, it can provide a more simple implementation method, and the obtained type I photosensitizer material has excellent performance and good universality.

[0010] The application adopts a wrapping strategy to combine a photosensitizer and a polymer matrix together by physical compounding to construct a type I photosensitizer material. The polymer matrix is an ionic polymer, which establishes a charged polymer aggregation microenvironment for the photosensitizer to induce electron transfer of the photosensitizer to generate efficient ROS. By designing the structure of the polymer matrix to control the microelectric field strength of the aggregation microenvironment, the excited state properties of the photosensitizer are controlled to realize the conversion of the photosensitizer to a type I photosensitizer.

[0011] The application of organic small molecule photosensitizers is faced with problems such as molecular hydrophobicity, poor in vivo distribution ability, potential biological toxicity, and the like. In addition, the small molecular volume is easy to be metabolized and excreted out of the body, and measures need to be taken to avoid these problems in application. Encapsulating the organic small molecule photosensitizer and other substances into nanoparticles becomes an important way to solve the above problems. Nanoparticles are more uniform in distribution in the body and are easier to accumulate in the lesion area, thereby improving the treatment efficiency. The carrier for encapsulating the photosensitizer can be liposomes, hydrogels, micelles, liquid crystals, polymers and the like. Selecting a suitable polymer to control a special aggregation microenvironment can control the excited state properties of the photosensitizer, provide electrons for the triplet exciton, promote the occurrence of electron transfer, and construct a nanoparticle type I photosensitizer material.

[0012] One of the purposes of the application is to provide a preparation method of a type I photosensitizer material, comprising:

[0013] The raw materials including a multi-block polymer having a hydrophobic segment and an ionic segment and a photosensitizer are dissolved in a solvent A, dispersed into water under the action of ultrasonic, and then treated to obtain the type I photosensitizer material.

[0014] In a preferred embodiment of the application,

[0015] The multi-block polymer having a hydrophobic segment and an ionic segment is one of a binary block polymer and a ternary block polymer;

[0016] The polymerization degree of the hydrophobic segment of the multi-block polymer having a hydrophobic segment and an ionic segment is 1-500, and is preferably 5-200;

[0017] The polymerization degree of the ionic segment of the multi-block polymer having a hydrophobic segment and an ionic segment is 1-500, and is preferably 5-200;

[0018] The photosensitizer is a hydrophobic photosensitizer molecule, and is preferably at least one of a porphyrin photosensitizer, an aggregation-induced emission photosensitizer, a BODIPY photosensitizer and a cyanine photosensitizer; the aggregation-induced emission photosensitizer is preferably a tetraphenylstyrene photosensitizer; and the porphyrin photosensitizer can be 5, 10, 15, 20-tetra(p-tolyl)porphyrin (TPTHP) and the like;

[0019] The solvent A is a polar solvent, preferably at least one of acetone, tetrahydrofuran, dimethyl sulfoxide, dimethyl formamide;

[0020] The water is deionized water.

[0021] In a preferred embodiment of the present application,

[0022] The mass ratio of the multi-block polymer with hydrophobic segment and ionic segment to photosensitizer is (0.1-20):1, preferably (0.5-10):1, and more preferably (1-5):1;

[0023] The ratio of the sum of the volume of the solvent A and water to the mass of the photosensitizer is (1-200) mL:1 mg, preferably (5-15) mL:1 mg;

[0024] The volume ratio of the solvent A to water is (0.01-2):1, preferably (0.05-1):1, and more preferably (0.05-0.2):1;

[0025] The dispersion is performed by dropwise addition or perfusion, and the dropwise addition or perfusion speed is 50-1000 μL / min, preferably 100-300 μL / min;

[0026] The post-treatment includes adjusting the pH value and hydrolysis; preferably, the pH value is adjusted to 7.1-11.0, preferably 8.0-9.0; and / or, the pH value is adjusted by an alkali solution, preferably a NaOH solution; and / or, the hydrolysis temperature is 20-80°C, preferably 40-60°C; and the hydrolysis time is 3-5 h.

[0027] The ultrasonic purpose is to promote the uniformity of the two-phase mixing in the experiment, so as to achieve the purpose of the nanoparticle size of 50-300 nm, and any device with ultrasonic dispersion function can achieve this purpose, preferably, the ultrasonic frequency is 30-50 kHz, and the ultrasonic time is 5-15 min.

[0028] In a preferred embodiment of the present application,

[0029] The multi-block polymer with hydrophobic segment and ionic segment is obtained by active radical polymerization, and the active radical polymerization is preferably reversible addition-fragmentation chain transfer (RAFT) polymerization;

[0030] Preferably, the hydrophobic segment of the multi-block polymer is obtained by polymerization of the oil-soluble monomer A and the oil-soluble monomer B, and the ionic segment of the multi-block polymer is obtained by polymerization of the ionic monomer or the monomer hydrolyzable into an ionic group;

[0031] Further preferably, the oil-soluble monomer A is firstly polymerized by reversible addition-fragmentation chain transfer (RAFT) to obtain a primary polymer; and the obtained primary polymer is used as a macroinitiator to copolymerize with an ionic monomer or a monomer hydrolyzable into an ionic group and an oil-soluble monomer B, so as to obtain the multi-block polymer by active radical polymerization.

[0032] In order to achieve the purpose of forming nanoparticles by wrapping photosensitizer molecules, the polymer molecular chain needs to have two parts of lipophilic segments and ionic segments, so the polymer is designed as an amphiphilic block polymer. Taking polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) as an example: firstly, polystyrene (PS) segments are prepared by RAFT polymerization with styrene as a monomer; and then the prepared PS is used as a macroinitiator to polymerize styrene and maleic anhydride monomers by RAFT polymerization, so as to finally prepare the block polymer PS-b-PMS.

[0033] In a preferred embodiment of the present application,

[0034] The preparation method of the multi-block polymer with hydrophobic segments and ionic segments is as follows:

[0035] (1) the RAFT reagent, the oil-soluble monomer A and the initiator A are dissolved in a solvent A', and a primary polymer is obtained by reaction;

[0036] (2) the ionic monomer or the monomer hydrolyzable into an ionic group, the obtained primary polymer and the initiator B, and the oil-soluble monomer B are dissolved in a solvent B to react, and the multi-block polymer with hydrophobic segments and ionic segments is obtained after post-treatment.

[0037] In a preferred embodiment of the present application,

[0038] The oil-soluble monomer A and the oil-soluble monomer B are each independently selected from at least one of methyl methacrylate, vinyl acetate, styrene, 4-methoxystyrene, 4-cyanostyrene, 4-vinylpyridine, 4-fluorostyrene, 4-chlorostyrene, 4-bromostyrene, 4-iodostyrene and sodium styrene sulfonate;

[0039] The ionic monomer or the monomer hydrolyzable into an ionic group is preferably at least one of acrylamide, isopropyl acrylamide, acrylic acid, crotonic acid, 4-vinylpyridine, sodium styrene sulfonate, methyl methacrylate, methyl methacrylate, 2,3-dimethyl maleic anhydride, maleic anhydride, citraconic anhydride, bromomaleic anhydride and chloromaleic anhydride.

[0040] In a preferred embodiment of the present application,

[0041] The RAFT agent is dithiocarbonates, trithiocarbonates, xanthates or dithiourethanes, more preferably trithiocarbonates, preferably at least one of 4-cyano-4-(dodecyltrithiocarbonate)pentanoic acid, 2-(dodecylthiothiocarbonylthio)-2-methylpropionic acid;

[0042] In which, 4-cyano-4-(dodecyltrithiocarbonate)pentanoic acid, referred to as CDTCP. The relative molecular mass of CDTCP is 403.17.

[0043]

[0044] The synthetic route is as follows:

[0045]

[0046] The initiator A and initiator B are independently selected from at least one of azobisisobutyronitrile, azobisisoheptyl nitrile, dimethyl azobisbutyrate, dibenzoyl peroxide, hydrogen peroxide, ammonium persulfate, potassium persulfate, benzoyl tert-butyl peroxide, methyl ethyl ketone peroxide;

[0047] The solvent A' and solvent B are independently selected from at least one of tetrahydrofuran, N,N-dimethylformamide, acetone, dimethyl sulfoxide.

[0048] In a preferred embodiment of the present application,

[0049] Step (1),

[0050] Oxygen can be removed before free radical copolymerization, and conventional operation mode of RAFT polymerization can be used, preferably freeze pumping mode to remove oxygen, specifically, freeze pumping three times before polymerization;

[0051] The molar ratio of the oil-soluble monomer A to the RAFT agent is (10-100):1, preferably (30-60):1;

[0052] The amount of initiator A is 0.1-100% of the molar amount of the RAFT agent, preferably 15-25%;

[0053] The volume of the solvent A' to the mass of the oil-soluble monomer A, the RAFT agent and the initiator is (1-10):1 uL / mg, preferably (2-3):1 uL / mg;

[0054] The reaction temperature is 40-120℃, preferably 50-90℃;

[0055] The reaction time is 6-96h, preferably 24-72h, more preferably 48-72h;

[0056] After reaction, washing and drying; preferably precipitating with organic solvent, centrifugal washing; the organic solvent is the commonly used organic solvent in the art, preferably at least one of methanol and ethyl acetate; drying can be the common drying method in the art, such as drying in a blast drying oven or a vacuum drying oven, and the temperature and time of drying are according to the common conditions in the art;

[0057] Step (2),

[0058] The molar ratio of the oil-soluble monomer B to the ionic monomer or the monomer hydrolyzable into ionic groups is (0.5-1.5):1, preferably (0.8-1.2):1;

[0059] The molar ratio of the oil-soluble monomer B to the primary polymer is (5-200):1, preferably (5-120):1;

[0060] The amount of the initiator B is 0.1-100% of the molar amount of the primary polymer, preferably 15-25%;

[0061] The volume ratio of the solvent B to the mass of the oil-soluble monomer B, the ionic monomer or the monomer hydrolyzable into ionic groups, the primary polymer and the initiator B is (1-10):1 uL / mg, preferably (1-4):1 uL / mg;

[0062] The reaction temperature is 40-120℃, preferably 50-90℃;

[0063] The reaction time is 6-96h, preferably 24-72h, more preferably 48-72h.

[0064] In a preferred embodiment of the present application,

[0065] The type I photosensitizer material is concentrated after ultrafiltration or dialysis, and the purpose of ultrafiltration or dialysis is to remove toxic organic solvents in the material.

[0066] The second object of the present application is to provide a type I photosensitizer material prepared by the above method.

[0067] The third object of the present application is to provide an application of a type I photosensitizer material in photodynamic therapy, photodynamic antibiosis and photocatalytic degradation of pollutants. The type I photosensitizer material prepared by the present application can generate reactive oxygen species by light to treat diseases, kill bacteria and fungi and degrade pollutants.

[0068] Compared with the prior art, the present application has the following beneficial effects:

[0069] The application provides a type I photosensitizer construction method based on polymer aggregation microenvironment construction and regulation. The type I photosensitizer material of the application is composed of a polymer matrix and a photosensitizer molecule. The polymer matrix molecular chain structure contains an ionic group, which functions to construct and regulate the polymer aggregation microenvironment; the photosensitizer molecule can be any molecule with photosensitization performance, which functions to absorb light energy to generate ROS. The combination of the polymer matrix and the photosensitizer molecule can be realized in the form of polymerization or wrapping to obtain a nanoscale photosensitizer material. The obtained photosensitizer material has significantly improved ROS generation performance, especially superoxide anion and hydroxyl radical. The photosensitizer material can generate strong ROS under normal oxygen and anoxic conditions, and has significant tumor growth inhibition and antibacterial performance.

[0070] The performance improvement of the photosensitizer material is mainly due to the effect of the characteristic aggregation microenvironment established by the polymer matrix material, which is mainly the ionic group to establish a microelectric field environment with rich electrostatic interaction. The obtained photosensitizer material structure contains two parts of polymer matrix and photosensitizer molecule, and the polymer matrix has a negative carboxyl group after hydrolysis, which constructs a polymer aggregation microenvironment with a microelectric field. The photosensitizer molecule is subjected to the aggregation and negative charge of the carboxyl group in the polymer matrix, which is conducive to inducing electron-hole separation to generate superoxide anion or hydroxyl radical.

[0071] The application proposes a characteristic aggregation microenvironment based on ionic groups to realize the regulation of the excited state performance of the photosensitizer molecule. The important factor is the ionic group in the polymer matrix material, which is independent of the photosensitizer molecule and the polymer-photosensitizer connection mode. Therefore, the concept or strategy has certain universality. BRIEF DESCRIPTION OF DRAWINGS

[0072] Figure 1 is a superoxide anion generation effect detection diagram of the type I photosensitizer material in Example 1;

[0073] H2O is water, TPTHP is a photosensitizer 5,10,15,20-tetra(p-tolyl)porphyrin, TPTHP+PS-b-PMS 6786 is a non-hydrolyzed nanoparticle, and TPTHP+HyPS-b-PMS 6786 is a hydrolyzed nanoparticle;

[0074] Figure 2 is a hydroxyl radical generation effect detection diagram of the type I photosensitizer material in Example 1;

[0075] H2O is water, TPTHP is a photosensitizer 5,10,15,20-tetra(p-tolyl)porphyrin, TPTHP+PS-b-PMS 6786 is a non-hydrolyzed nanoparticle, and TPTHP+HyPS-b-PMS 6786 is a hydrolyzed nanoparticle;

[0076] Figure 3 is the particle size and transmission electron micrograph of the Type I photosensitizer material in Example 1;

[0077] TPTHP+HyPS-b-PMS 6786 is a hydrolyzed nanoparticle;

[0078] Figure 4 is the nuclear magnetic hydrogen spectrum of the polymer TPTHP+PS-b-PMS 6786 in Example 1;

[0079] Figure 5 is the infrared spectrum of the polymer TPTHP+PS-b-PMS 6786 in Example 1;

[0080] Figure 6 is the gel permeation chromatography (GPC) curve of PS-b-PMS in Example 1. DETAILED DESCRIPTION

[0081] The present application will be described in detail below with specific reference to the drawings and embodiments. It is necessary to point out here that the following embodiments are only used to further illustrate the present application, and cannot be understood as limiting the scope of protection of the present application. Some non-essential improvements and adjustments made by those skilled in the art based on the content of the present application are still within the scope of protection of the present application.

[0082] The CDTCP used in the examples is synthesized by the laboratory itself, and the remaining raw materials are all conventional commercially available raw materials.

[0083] Synthesis of CDTCP:

[0084]

[0085] The full name of CDTCP is 4-cyano-4-(dodecyltrithiocarbonate) pentanoic acid, which participates in the reaction as a RAFT reagent, and is synthesized according to the method proposed by Sheehan et al. [Sheehan M T, Farnham W B, Okazaki H, et al. RAFT technology for the production of advanced photoresist polymers [C] / / Advances in Resist Materials and Processing Technology XXV. SPIE, 2008, 6923: 746-754.].

[0086] CDTCP is synthesized by two-step reaction, and the operation is as shown below.

[0087] The first step reaction is dodecyl mercaptan and carbon disulfide according to 1:1 feeding ratio. The specific experimental steps are as follows: under the condition of ice water mixed bath, 200 mL of n-hexane is added into the flask, and then 35 mL of THF solution dissolved with potassium tert-butoxide (6.98 g) is added. When the temperature is increased to 5°C, 12.14 g of dodecyl mercaptan is added, and after keeping at 5°C for 30 min, 4.72 g of carbon disulfide is slowly added dropwise, and stirred for 10 min. After stirring at room temperature for 4 h, 25 mL of THF solution dissolved with 8.02 g of iodine is added dropwise. After stirring at room temperature for 15 h, the reaction is completed, and 20 mL of water is added to quench the reaction. THF is removed by rotary evaporation, and the organic phase is extracted with saturated NaCl solution and saturated sodium thiosulfate solution for three times. After drying, the organic phase is rotary evaporated and oven dried to obtain 15.25 g of red-brown oily substance.

[0088] The second step reaction is to dissolve 15.25 g of red-brown oily substance in 100 mL of ethyl acetate and add it into the flask, and then reflux at 70°C. 50 mL of ethyl acetate solution dissolved with 11.10 g of 4,4'-azobis(4-cyanopentanoic acid) is slowly added, and the reaction is carried out for 16 h. After the reaction is completed, the ethyl acetate is removed by rotary evaporation, and the product is in oily state. N-hexane is added for washing, and then filtered, followed by water washing to obtain a solid. The solid is dissolved with ethyl acetate, filtered, and the clear filtrate is collected. The filtrate is rotary evaporated to obtain red-brown oily product. After oven drying, yellow-green powder (easily changed to liquid by heating) product is obtained.

[0089] Test method:

[0090] 1. Infrared spectroscopy test: the functional group characteristic peaks are characterized by Fourier infrared spectroscopy (FTIR). The sample is freeze-dried into powder for FTIR test. The sample is prepared by KBr pressing method, a small amount of sample powder and KBr are mixed and ground in a mortar, and then pressed into a sheet. The infrared signal is collected, and the collection range is 400-4000 cm -1 .

[0091] 2. Nuclear magnetic hydrogen spectrum test: for confirmation of structure, the polymer is washed, dried, and then characterized by H NMR using deuterated acetone as solvent. 1

[0092] 3. Gel permeation chromatography (GPC) test: for mastering the molecular weight of the polymer, the polymer PS and PS-b-PMS are washed, centrifuged, and dried to obtain dry polymer powder for GPC test.

[0093] 4. For mastering the particle size of the material in liquid, the particle size is tested by dynamic light scattering instrument (DLS), the sample is diluted to 1×10 -5 mol / L, 3 mL of which is added into a quartz dish, and the DLS test is carried out to obtain the particle size information of the material.

[0094] ​5. Transmission electron microscope test, disperse the sample in the corresponding solvent (the solvent used for reaction or the solvent used for preparation), use a pipette to add 10 μL of sample liquid to a copper mesh, repeat twice, and test the transmission electron microscope after drying;

[0095] 6. Test the ROS production capacity of the sample using an indicator, and the indicators are DHR123 and HPF, which are used to test superoxide anion and hydroxyl radical respectively. The specific process of the test is as follows: first, prepare the test solution, and mix the sample to be tested, the indicator (DHR123 or HPF) and water to prepare a 2 mL test solution, wherein the sample concentration is 1 × 10 -5 mol / L, and the DHR123 or HPF concentration is 1 × 10 -5 mol / L. Add 2 mL of the test solution to a quartz dish, and place it under the light of a LED light source 660 nm red light source (25 mW / cm 2 ) for 10 min, and test the fluorescence intensity every 1 min (the excitation wavelength of DHR123 is 500 nm, and the collection range is 510-560 nm; the excitation wavelength of HPF is 492 nm, and the collection range is 500-550 nm). The fluorescence intensity at the characteristic emission wavelength (the characteristic emission wavelength of DHR123 is 529 nm, and the characteristic emission wavelength of HPF is 515 nm) is recorded as I, and the fluorescence intensity value at 0 min is recorded as I0, and the I / I0-1 data is obtained.

[0096] Example 1

[0097] Preparation of a multi-block polymer having a hydrophobic segment and an ionic segment:

[0098]

[0099] Preparation of polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) by RAFT polymerization, and the reaction solvent is selected as tetrahydrofuran.

[0100] The reaction raw materials styrene (2000 μL, 1818 mg, 17.46 mmol), RAFT reagent CDTCP (140.95 mg, 0.350 mmol) and initiator AIBN (11.47 mg, 0.070 mmol) were dissolved in 5100 μL of tetrahydrofuran and transferred to a Schlenk tube. The air in the reaction system was removed by freeze-pumping, the tube was frozen in liquid nitrogen for 5 min and pumped for 5 min. The freeze-pumping was repeated three times. Then the Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The polymer was precipitated by methanol / ethyl acetate, washed by centrifugation, and placed in a 70 °C air-drying oven for 24 h, and then placed in a 60 °C vacuum drying oven for 24 h to obtain dry PS (the number average molecular weight was 2943 g / mol).

[0101] Further polymerization was carried out by dissolving the obtained PS (100.00 mg, 0.034 mmol), styrene (97.2 μL, 0.848 mmol, 88 mg), maleic anhydride (MAH, 83.30 mg, 0.849 mmol) and initiator azobisisobutyronitrile (AIBN, 1.20 mg, 0.007 mmol) in tetrahydrofuran (1 mL) and transferring to a Schlenk tube. The air in the reaction system was removed by freeze-pumping, the tube was frozen in liquid nitrogen for 5 min and pumped for 5 min. The freeze-pumping was repeated three times. The Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The PS-b-PMS was precipitated, centrifuged and washed by petroleum ether / ethyl acetate. The washed polymer was placed in a 70 °C air-drying oven for 24 h, and then placed in a 60 °C vacuum drying oven for 24 h to obtain dry PS-b-PMS 6786 (the number average molecular weight of the PS segment was 2943 g / mol, and the number average molecular weight of the PMS segment was 3843 g / mol).

[0102] Preparation of type I photosensitizer material:

[0103] The type I photosensitizer material in the form of nanoparticles was prepared by coating the obtained PS-b-PMS 6786 with an organic small molecule photosensitizer.

[0104] The 5,10,15,20-tetra(p-tolyl)porphyrin (TPTHP, CAS: 14527-51-6) was chosen as photosensitizer, and the prepared PS-b-PMS 6786 was used to encapsulate the photosensitizer to prepare nanoparticles by nanoco-precipitation method. The PS-b-PMS 6786 and TPTHP were prepared into nanoparticles at the same molar ratio, and the molar ratio was TPTHP: PS-b-PMS = 5:1. 1 mg of TPTHP and 2.00 mg of PS-b-PMS 6786 (2943-3843) were weighed and nanoparticles were prepared by nanoco-precipitation method: TPTHP and polymer were dissolved together in 1 mL of fresh tetrahydrofuran, and 1 mL of tetrahydrofuran mixture was slowly dispersed into 9 mL of deionized water under the action of ultrasonic wave of large ultrasonic machine using a perfusion machine, and a Shumei numerical control ultrasonic cleaner KQ-500DE was used, the ultrasonic frequency was 40 kHz, the ultrasonic temperature was 20-30°C, and the total volume of the solution was 10 mL. The perfusion speed was 200 μL / min, the perfusion time was about 5 min, and the ultrasonic time was 10 min after the perfusion was completed. 5 mL of the obtained liquid was taken out, 20 μL of NaOH solution (0.2 mol / L) was added to adjust the pH to about 9 and maintain it unchanged, and hydrolysis was carried out at 50°C for 4 h. The target product nanoparticle photosensitizer was obtained after hydrolysis. TPTHP+PS-b-PMS 6786 is unhydrolyzed nanoparticle, and TPTHP+HyPS-b-PMS 6786 is hydrolyzed nanoparticle.

[0105] The number average molecular weight of PS and PS-b-PMS was characterized by gel permeation chromatography (GPC) as 2943, 6786 g / mol. PS and PS-b-PMS were characterized by nuclear magnetic hydrogen spectrum, which reflected that the polymerization degree of PS was 24, and the polymerization degree of PS-b-PMS was 24-b-19. The molecular weight of the two was calculated by nuclear magnetic hydrogen spectrum as 2902, 6750 g / mol, which matched the GPC data. It was proved that the block polymer was successfully prepared. DLS and transmission electron microscopy showed that the particle size of the prepared nanoparticles was 251.88 nm, and the nanoparticles had spherical morphology. The indicator test ROS experiment showed that the nanoparticles TPTHP+PS-b-PMS 6786 and TPTHP+HyPS-b-PMS 6786 had superoxide anion production capacity under light, and TPTHP+HyPS-b-PMS 6786 had obvious hydroxyl radical production capacity.

[0106] Example 2

[0107] Preparation of multi-block polymer with hydrophobic segment and ionic segment:

[0108] Polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) was prepared by RAFT polymerization, in which the PS (number average molecular weight 2943 g / mol) was prepared in the same way as Example 1.

[0109] Further polymerization was carried out by dissolving the obtained PS (100.00 mg, 0.034 mmol), styrene (194.40 μL, 1.697 mmol, 176.71 mg), MAH (1.70 mmol, 166.60 mg) and initiator AIBN (0.007 mmol, 1.20 mg) in tetrahydrofuran (1 mL) and transferring into a Schlenk tube. The air in the reaction system was removed by freeze-thaw degassing, the tube was frozen in liquid nitrogen for 5 min and vacuumed for 5 min. The freeze-thaw degassing step was repeated three times. The Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The PS-b-PMS was precipitated, centrifuged and washed by petroleum ether / ethyl acetate. The washed polymer was placed in a 70 °C air-drying oven for 24 h and then in a 60 °C vacuum drying oven for 24 h to obtain the dried PS-b-PMS 10113 (PS segment number average molecular weight 2943, PMS segment number average molecular weight 7170).

[0110] Preparation of type I photosensitizer material:

[0111] Nanoparticles were prepared by encapsulating organic small molecule photosensitizer with polymer matrix. 5,10,15,20-Tetra(p-tolyl)porphyrin (TPTHP, CAS: 14527-51-6) was selected as photosensitizer, and the prepared PS-b-PMS 10113 was used to encapsulate the photosensitizer to prepare nanoparticles by nanoprecipitation method. The PS-b-PMS 10113 and TPTHP were prepared into nanoparticles at the same molar ratio, and the molar ratio was TPTHP:PS-b-PMS=5:1. 1 mg of TPTHP and 2.98 mg of PS-b-PMS 10113 were weighed and nanoparticles were prepared by nanoprecipitation method: TPTHP and polymer were dissolved together in 1 mL (0.89 g) of fresh tetrahydrofuran, and 1 mL of tetrahydrofuran mixture was slowly dispersed into 9 mL of deionized water under the action of ultrasonic wave of large ultrasonic machine using a perfusion machine, and the total volume of the solution was 10 mL. The perfusion machine speed was 200 μL / min, the perfusion time was about 5 min, and the ultrasonic time was 10 min after the perfusion was completed. Then 5 mL of nanoparticles was taken out, 20 μL of NaOH solution (0.2 mol / L) was added to adjust the pH to about 9 and maintain it unchanged, and hydrolysis was carried out at 50 °C for 4 h. Type I photosensitizer material was obtained after hydrolysis.

[0112] Example 3

[0113] Preparation of multi-block polymer with hydrophobic segment and ionic segment:

[0114] Polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) was prepared by RAFT polymerization, in which the step of preparing PS (number average molecular weight 2943 g / mol) was the same as Example 1.

[0115] Further polymerization was carried out by dissolving the obtained PS (100.00 mg, 0.034 mmol), styrene (291.60 μL, 2.545 mmol, 265.06 mg), MAH (2.548 mmol, 249.90 mg) and initiator AIBN (1.20 mg) in tetrahydrofuran (1 mL) and transferring into a Schlenk tube. The air in the reaction system was removed by freeze-thaw degassing, the tube was frozen in liquid nitrogen for 5 min and vacuumed for 5 min. The freeze-thaw degassing step was repeated three times. The Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The PS-b-PMS was precipitated, centrifuged and washed by petroleum ether / ethyl acetate. The washed polymer was placed in a 70 °C air-drying oven for 24 h and then in a 60 °C vacuum drying oven for 24 h to obtain dried PS-b-PMS 13648 (PS segment number average molecular weight 2943, PMS segment number average molecular weight 10705).

[0116] Preparation of type I photosensitizer material:

[0117] Nanoparticles were prepared by encapsulating organic small molecule photosensitizer with polymer matrix. 5,10,15,20-Tetra(p-tolyl)porphyrin (TPTHP, CAS: 14527-51-6) was chosen as photosensitizer, and PS-b-PMS 13648 was used to encapsulate the photosensitizer to prepare nanoparticles by nanoprecipitation method. Nanoparticles were prepared with PS-b-PMS 13648 and TPTHP in the same molar ratio, molar ratio of TPTHP: PS-b-PMS = 5: 1. 1 mg TPTHP and 4.02 mg PS-b-PMS 13648 were weighed and nanoparticles were prepared by nanoprecipitation method: TPTHP and polymer were dissolved together in 1 mL (0.89 g) of fresh tetrahydrofuran, and 1 mL of tetrahydrofuran mixture was slowly dispersed into 9 mL of deionized water under the action of ultrasonic wave of large ultrasonic machine using perfusion machine, using Shumei numerical control ultrasonic cleaner KQ-500DE, ultrasonic frequency was 40 kHz, ultrasonic temperature was 20-30 °C, total volume of solution was 10 mL. The perfusion machine speed was 200 μL / min, the perfusion time was about 5 min, and the ultrasonic time was 10 min after perfusion. Then 5 mL of nanoparticles were taken out, 20 μL of NaOH solution (0.2 mol / L) was added to adjust the pH to about 9 and maintain it, and hydrolysis was carried out at 50 °C for 4 h. The target product nanoparticle photosensitizer was obtained after hydrolysis.

[0118] Example 4

[0119] Preparation of multi-block polymer with hydrophobic segment and ionic segment:

[0120] The method for preparing nanoparticle photosensitizer material is as follows:

[0121] Polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) was prepared by RAFT polymerization, in which the preparation of PS (number average molecular weight 2943 g / mol) was the same as in Example 1.

[0122] Further polymerization was carried out by dissolving the obtained PS (100.00 mg, 0.034 mmol), styrene (388.80 μL, 3.393 mmol, 353.42 mg), MAH (3.398 mmol, 333.20 mg) and initiator AIBN (1.20 mg) in tetrahydrofuran (1 mL) and transferring into a Schlenk tube. The air in the reaction system was removed by freeze-thaw degassing, the tube was frozen in liquid nitrogen for 5 min and vacuumed for 5 min. The freeze-thaw degassing step was repeated three times. The Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The PS-b-PMS was precipitated, centrifuged and washed by petroleum ether / ethyl acetate. The washed polymer was placed in a 70 °C air-drying oven for 24 h and then in a 60 °C vacuum drying oven for 24 h to obtain dried PS-b-PMS15013 (the number average molecular weight of the PS segment was 2943 and the number average molecular weight of the PMS segment was 12070).

[0123] Preparation of type I photosensitizer material:

[0124] Nanoparticles were prepared by encapsulating organic small molecule photosensitizer with polymer matrix. 5,10,15,20-Tetra(p-tolyl)porphyrin (TPTHP, CAS: 14527-51-6) was selected as photosensitizer and the prepared PS-b-PMS 13648 was used to encapsulate the photosensitizer into nanoparticles by nanoprecipitation method. PS-b-PMS 15013 was used to encapsulate TPTHP into nanoparticles at the same molar ratio, the molar ratio of TPTHP: PS-b-PMS was 5:1. 1 mg TPTHP and 4.42 mg PS-b-PMS 15013 were weighed and nanoparticles were prepared by nanoprecipitation method: TPTHP and polymer were dissolved in 1 mL (0.89 g) of fresh tetrahydrofuran, 1 mL of tetrahydrofuran mixture was slowly dispersed into 9 mL of pure water under the action of ultrasound of a large ultrasonic machine using a perfusion machine, a Shumei numerical control ultrasonic cleaner KQ-500DE was used, the ultrasonic frequency was 40 kHz and the ultrasonic temperature was 20-30 °C, the total volume of the solution was 10 mL. The perfusion speed was 200 μL / min and the perfusion time was about 5 min, the ultrasonic time was 10 min in total. Then 5 mL of nanoparticles were taken out, 20 μL of NaOH solution (0.2 mol / L) was added to adjust the pH to about 9 and maintain it unchanged, and the hydrolysis was carried out at 50 °C for 4 h. The target product, nanoparticle photosensitizer, was obtained after hydrolysis.

[0125] Example 5

[0126] Preparation of multi-block polymer with hydrophobic segment and ionic segment:

[0127] Polystyrene-b-poly(styrene-alt-maleic anhydride) (PS-b-PMS) was prepared by RAFT polymerization, in which the PS (number average molecular weight 2943 g / mol) was prepared in the same way as Example 1.

[0128] Further polymerization was carried out by dissolving PS (200.00 mg, 0.034 mmol), St (37.40 μL, 0.326 mmol, 34.00 mg), MAH (0.326 mmol, 32.00 mg) and initiator AIBN (2.14 mg) in tetrahydrofuran (1 mL) and transferring into a Schlenk tube. The air in the reaction system was removed by freeze-thaw degassing, the tube was frozen in liquid nitrogen for 5 min and vacuumed for 5 min. The freeze-thaw degassing step was repeated three times. The Schlenk tube was placed in a 70 °C oil bath with magnetic stirring at 200 r / min for 72 h. The PS-b-PMS was precipitated, centrifuged and washed by petroleum ether / ethyl acetate. The washed polymer was placed in a 70 °C air-drying oven for 24 h and then in a 60 °C vacuum drying oven for 24 h to obtain dried PS-b-PMS 4458 (PS segment number average molecular weight 2943, PMS segment number average molecular weight 1515).

[0129] Preparation of type I photosensitizer material:

[0130] Nanoparticles were prepared by encapsulating organic small molecule photosensitizer with polymer matrix. 5,10,15,20-Tetra(p-tolyl)porphyrin (TPTHP, CAS: 14527-51-6) was selected as photosensitizer and the prepared PS-b-PMS 4458 was used to encapsulate the photosensitizer to prepare nanoparticles by nanoprecipitation method. The PS-b-PMS 4458 and TPTHP were used to prepare nanoparticles in the same molar ratio, TPTHP:PS-b-PMS=5:1. 1 mg TPTHP and 1.31 mg PS-b-PMS 4458 were weighed and used to prepare nanoparticles by nanoprecipitation method: TPTHP and polymer were dissolved in 1 mL (0.89 g) of fresh tetrahydrofuran, 1 mL of tetrahydrofuran mixture was slowly dispersed into 9 mL of pure water under the action of ultrasonic wave of large ultrasonic machine using a perfusion machine, and the total volume of the solution was 10 mL. The ultrasonic frequency was 40 kHz and the ultrasonic temperature was 20-30 °C. The perfusion speed was 200 μL / min and the perfusion time was about 5 min. After perfusion, the ultrasonic time was continued for 5 min, and the total ultrasonic time was 10 min. Then 5 mL of nanoparticles were taken out, 20 μL of NaOH solution (0.2 mol / L) was added to adjust the pH to about 9 and maintain it unchanged, and hydrolysis was carried out at 50 °C for 4 h. The target product, nanoparticle photosensitizer, was obtained after hydrolysis.

[0131] Figure 1is the superoxide anion production effect detection diagram of type I photosensitizer materials TPTHP+PS-b-PMS 6786 and TPTHP+HyPS-b-PMS 6786 in Example 1; from Figure 1 It can be seen from the figure that TPTHP hardly produces superoxide anion, and TPTHP+PS-b-PMS 6786 and TPTHP+HyPS-b-PMS 6786 can produce superoxide anion, and I / I0-1 reaches 7.13 and 10.22 respectively under light for 10 min. The superoxide anion data show that TPTHP+PS-b-PMS 6786 and TPTHP+HyPS-b-PMS 6786 produce reactive oxygen species through type I electron transfer process, and the polymer-encapsulated photosensitizer promotes the electron transfer process, and the type I photosensitizer is successfully constructed.

[0132] Figure 2 is the hydroxyl radical production effect detection diagram of type I photosensitizer materials TPTHP+PS-b-PMS 6786 and TPTHP+HyPS-b-PMS 6786 in Example 1; from Figure 2 It can be seen from the figure that TPTHP hardly produces hydroxyl radical, TPTHP+PS-b-PMS 6786 has general hydroxyl radical production ability (I / I0-1 reaches 3.90 under light for 10 min), and TPTHP+HyPS-b-PMS 6786 has strong hydroxyl radical production ability (I / I0-1 reaches 46.12 under light for 10 min). The polymer-encapsulated induces the photosensitizer to produce superoxide anion through type I electron transfer process, and the hydroxyl radical is produced after the hydrolysis of the introduced carboxyl group. Among the three materials, TPTHP+HyPS-b-PMS 6786 has better photosensitizing effect, and can produce superoxide anion and hydroxyl radical at the same time. This shows that the type I photosensitizer material is successfully constructed, and the hydrolysis of the nanoparticles can produce hydroxyl radical.

[0133] Figure 3 is the particle size and transmission electron microscope image of the type I photosensitizer material in Example 1; from the figure, it can be seen that the dynamic light scattering instrument (DLS) and the scanning electron microscope show that the prepared hydrolyzed nanoparticles have a particle size of 251.88 nm and are spherical nanoparticles.

[0134] Figure 4 is the nuclear magnetic resonance spectrum of the polymer TPTHP+PS-b-PMS 6786 in Example 1, the chemical shift δ=6-8 ppm corresponds to H on the benzene ring, 0.88 ppm indicates H of the terminal methyl group at b in the structural formula, and δ=3-3.8 ppm indicates H on the MAH methine group of the PMS segment at c. The integral number ratio of H at positions a, b and c is 214.81:3:38.17, and it is calculated that the polymerization degree of PS is 24 and the polymerization degree of PS-b-PMS is 24-b-19.

[0135] Figure 5 is the infrared spectrum of the polymer TPTHP+PS-b-PMS 6786 in Example 1. 701, 1602, 1495, 1454 cm -1 is the C=O bond symmetric stretching vibration absorption peak of MAH; 1774, 1855 cm -1 is the C=O bond symmetric stretching vibration absorption peak of MAH; 1221 cm -1 is the five-membered ring structure absorption peak of MAH; it can be seen from the infrared spectrum that there are anhydride groups and benzene rings in the structure of PS-b-PMS, and the block copolymer is successfully copolymerized.

[0136] Figure 6 is the gel permeation chromatography (GPC) curve of PS-b-PMS in Example 1, and the GPC data show that the number average molecular weight of PS-b-PMS is 6786 g / mol. The number average molecular weights of PS and PS-b-PMS are 2943 and 6786 g / mol, respectively, as characterized by GPC, which reflects that the polymerization degree of PS is 24 and the polymerization degree of PS-b-PMS is 24-b-19. The polymerization degrees of PS and PS-b-PMS are calculated to be 24 and 24-b-19, respectively, as characterized by nuclear magnetic hydrogen spectrum, which is matched with the GPC data. It is proved that the block polymer is successfully prepared.

[0137] The type I photosensitizer material prepared in Examples 1-5 has superoxide anion generation capacity and hydroxyl radical generation capacity under light irradiation, which proves that the type I photosensitizer based on the construction and regulation of polymer aggregation microenvironment can generate strong ROS under normoxic and anoxic conditions, has the performance of significantly inhibiting tumor growth and antibacterial, and can be applied to the fields of photodynamic therapy, photodynamic antibacterial, and photocatalytic pollutant degradation.

Claims

1. A method for preparing a type I photosensitizer material, comprising: dissolving raw materials including a multi-block polymer having a hydrophobic segment and an ionic segment and a photosensitizer in a solvent A, dispersing the raw materials into water under the action of ultrasonic, and obtaining the type I photosensitizer material after post-treatment; the post-treatment comprises adjusting a pH value and hydrolysis; the pH value is adjusted to 7.1-11.0; the hydrolysis temperature is 20-80 ℃; and the hydrolysis time is 3-5 h; the multi-block polymer having the hydrophobic segment and the ionic segment is obtained by a method comprising: first, obtaining a primary polymer by reversible addition-fragmentation chain transfer polymerization of an oil-soluble monomer A; and then, copolymerizing the obtained primary polymer, an ionic monomer or a monomer that can be hydrolyzed into an ionic group, and an oil-soluble monomer B to obtain the multi-block polymer by active radical polymerization; the oil-soluble monomer A and the oil-soluble monomer B are styrene; and the ionic monomer or the monomer that can be hydrolyzed into an ionic group is maleic anhydride. 2.The method of claim 1, wherein: the multi-block polymer having the hydrophobic segment and the ionic segment is one of a binary block polymer; and / or, the polymerization degree of the hydrophobic segment of the multi-block polymer having the hydrophobic segment and the ionic segment is 1-500; and / or, the polymerization degree of the ionic segment of the multi-block polymer having the hydrophobic segment and the ionic segment is 1-500; and / or, the photosensitizer is a hydrophobic photosensitizer molecule; and / or, the solvent A is a polar solvent; and / or, the water is deionized water. 3.The method of claim 2, wherein: the polymerization degree of the hydrophobic segment of the multi-block polymer having the hydrophobic segment and the ionic segment is 5-200; and / or, the polymerization degree of the ionic segment of the multi-block polymer having the hydrophobic segment and the ionic segment is 5-200; and / or, the photosensitizer is at least one of a porphyrin photosensitizer, an aggregation-induced emission photosensitizer, a BODIPY photosensitizer, and a cyanine photosensitizer; and / or, the solvent A is at least one of acetone, tetrahydrofuran, dimethyl sulfoxide, and dimethylformamide. 4.The method of claim 3, wherein: the aggregation-induced emission photosensitizer is a tetraphenylstyrene photosensitizer. 5.The method of claim 1, wherein: the mass ratio of the multi-block polymer having the hydrophobic segment and the ionic segment to the photosensitizer is (0.1-20) : 1; and / or, the ratio of the sum of the volumes of the solvent A and the water to the mass of the photosensitizer is (1-200) mL : 1 mg; and / or, the volume ratio of the solvent A to the water is (0.01-2) : 1; and / or, the dispersion is performed by dropwise adding or perfusion at a speed of 50-1000 μL / min; and / or, the pH value is adjusted to 8.0-9.0; and / or, the pH value is adjusted by an alkali solution; and / or, the hydrolysis temperature is 40-60 ℃. 6.The method of claim 5, wherein: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ The mass ratio of the multi-block polymer with hydrophobic segment and ionic segment to photosensitizer is (0.5-10):1; and / or, The ratio of the sum of the volume of the solvent A and water to the mass of the photosensitizer is (5-15) mL:1 mg; and / or, The volume ratio of the solvent A to water is (0.05-1):1; and / or, The dispersion is performed by dropwise adding or perfusion, and the speed of dropwise adding or perfusion is 100-300 μL / min; and / or, The pH value is adjusted by a base solution, and the base solution is NaOH solution.

7. The preparation method of the type I photosensitizer material according to claim 6, characterized in that: The mass ratio of the multi-block polymer with hydrophobic segment and ionic segment to photosensitizer is (1-5):1; and / or, The volume ratio of the solvent A to water is (0.05-0.2):

1.

8. The preparation method of the type I photosensitizer material according to claim 1, characterized in that: The preparation method of the multi-block polymer with hydrophobic segment and ionic segment is: (1) dissolving the RAFT reagent, oil-soluble monomer A and initiator A in solvent A', and obtaining a primary polymer by reaction; (2) dissolving the ionic monomer or monomer hydrolyzable into ionic group, the obtained primary polymer and initiator B, and oil-soluble monomer B in solvent B, and obtaining the multi-block polymer with hydrophobic segment and ionic segment by reaction and post-treatment.

9. The preparation method of the type I photosensitizer material according to claim 8, characterized in that: The RAFT reagent is dithiocarbonic ester, trithiocarbonic ester, xanthate or dithiourethane; and / or, The initiator A and initiator B are independently selected from at least one of azobisisobutyronitrile, azobisisoheptyl nitrile, dimethyl azobis isobutyrate, dibenzoyl peroxide, hydrogen peroxide, ammonium persulfate, potassium persulfate, benzoyl tert-butyl peroxide and methyl ethyl ketone peroxide; and / or, The solvent A' and solvent B are independently selected from at least one of tetrahydrofuran, N, N-dimethylformamide, acetone and dimethyl sulfoxide.

10. The preparation method of the type I photosensitizer material according to claim 9, characterized in that: The trithiocarbonic ester is at least one of 4-cyano-4-(dodecyltrithiocarbonic ester) valeric acid and 2-(dodecylthiothiocarbonylthio)-2-methylpropionic acid.

11. The preparation method of the type I photosensitizer material according to claim 8, characterized in that: In step (1), Oxygen is removed before radical copolymerization; and / or, The molar ratio of the oil-soluble monomer A to the RAFT reagent is (10-100):1; and / or, The amount of the initiator A is 0.1-100% of the molar amount of the RAFT reagent; and / or, The ratio of the volume of the solvent A' to the mass sum of the oil-soluble monomer A, the RAFT reagent and the initiator is (1-10):1 uL / mg; and / or, The reaction temperature is 40-120 ℃; and / or, The reaction time is 6-96 h; and / or, After reaction, washing and drying are performed; and / or, In step (2), The molar ratio of the oil-soluble monomer B to the ionic monomer or the monomer hydrolyzable into ionic groups is (0.5-1.5):1; and / or, The molar ratio of the oil-soluble monomer B to the primary polymer is (5-200):1; and / or, The amount of the initiator B is 0.1-100% of the molar amount of the primary polymer; and / or, The volume of the solvent B to the mass of the oil-soluble monomer B, the ionic monomer or the monomer hydrolyzable into ionic groups, the primary polymer, and the initiator B is (1-10):1 uL / mg; and / or, The reaction temperature is 40-120 ℃; and / or, The reaction time is 6-96 h.

12. The preparation method of the type I photosensitizer material according to claim 11, characterized in that: Step (1), The molar ratio of the oil-soluble monomer A to the RAFT agent is (30-60):1; and / or, The amount of the initiator A is 15-25% of the molar amount of the RAFT agent; and / or, The volume of the solvent A' to the mass of the oil-soluble monomer A, the RAFT agent, and the initiator is (2-3):1 uL / mg; and / or, The reaction temperature is 50-90 ℃; and / or, The reaction time is 24-72 h; and / or, After the reaction, the organic solvent is used for precipitation, centrifugal washing; and / or, Step (2), The molar ratio of the oil-soluble monomer B to the ionic monomer or the monomer hydrolyzable into ionic groups is (0.8-1.2):1; and / or, The molar ratio of the oil-soluble monomer B to the primary polymer is (5-120):1; and / or, The amount of the initiator B is 15-25% of the molar amount of the primary polymer; and / or, The volume of the solvent B to the mass of the oil-soluble monomer B, the ionic monomer or the monomer hydrolyzable into ionic groups, the primary polymer, and the initiator B is (1-4):1 uL / mg; and / or, The reaction temperature is 50-90 ℃; and / or, The reaction time is 24-72 h.

13. The preparation method of the type I photosensitizer material according to claim 12, characterized in that: Step (1), The reaction time is 48-72 h; and / or, Step (2), The reaction time is 48-72 h.

14. The type I photosensitizer material prepared by the preparation method according to any one of claims 1-13.

15. The use of the type I photosensitizer material according to claim 14 in the preparation of photodynamic therapy drugs, the preparation of photodynamic antibacterial drugs, and the photocatalytic degradation of pollutants.

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