CN112336856B

CN112336856B - Organic NIR-II photo-thermal conversion film and preparation method and application thereof

Info

Publication number: CN112336856B
Application number: CN202010974648.4A
Authority: CN
Inventors: 陈卓; 许洁琼; 尹志威; 张良; 董倩
Original assignee: Hunan University
Current assignee: Hunan University
Priority date: 2020-09-16
Filing date: 2020-09-16
Publication date: 2021-09-17
Anticipated expiration: 2040-09-16
Also published as: CN112336856A

Abstract

The invention relates to an organic NIR-II photothermal conversion film and a preparation method and application thereof. The organic NIR-II photothermal conversion membrane is a hydrogen bond aggregate formed by hydrogen bond interaction between 3,3 ', 5, 5' -tetramethyl benzidine oxide and agarose. The preparation method comprises the following steps: 1) carrying out oxidation reaction on the 3,3 ', 5, 5' -tetramethylbenzidine mother solution in the presence of nano-enzyme catalysis and a buffer solution to obtain a nano-enzyme/3, 3 ', 5, 5' -tetramethylbenzidine oxide composite solution; 2) mixing the composite solution with agarose and heating to obtain sol; 3) and (3) preparing the sol into a film to obtain the organic NIR-II photothermal conversion film. The organic NIR-II photothermal conversion film has good uniformity, stable property and excellent NIR-II photothermal conversion efficiency, and the initial heating rate is as high as 30 ℃/s.

Description

Organic NIR-II photo-thermal conversion film and preparation method and application thereof

Technical Field

The invention belongs to the technical field of functional material preparation, and particularly relates to an organic NIR-II photo-thermal conversion film, and a preparation method and application thereof.

Background

Near Infrared (NIR) light is widely used in the fields of sensing, imaging, biological diagnostics and therapy because of its incomparable advantages of remote control, minimal intrusion, high transparency, etc. in "bio-windows". Among near-infrared absorbing materials, photothermal agents are materials that can convert near-infrared light energy into heat energy, and have attracted attention because they utilize near-infrared light energy conveniently and efficiently. Recently, the photothermal conversion of the second near infrared optical window (NIR-II, 1000-. The NIR-II light has wide application prospects in treating deep tissue buried diseases or providing energy for subcutaneous implantable bioelectronic devices. Therefore, the development of NIR-II photothermal materials has important clinical significance.

However, currently there are only a few NIR-II photothermal materials have been demonstrated to include inorganic photothermal materials such as non-geometric gold nanoparticles and mixed nanosystems, Fe₃O₄@ CuS-PEG nanoparticles, tungsten ammonium bronze nanotubes, and the like. Compared with inorganic materials, organic materials generally have overwhelming advantages of easy modification, good biocompatibility, potential biodegradability and the like. However, the development of organic NIR-ii photothermal materials is still in the beginning stage, and especially efficient NIR-ii photothermal conversion materials are seriously deficient. Therefore, the development of efficient organic NIR-ii photothermal materials is an urgent need for biological applications. Zhang et al utilize N, N-dimethyl bipyridyl thiazolothiazole (MPT)²⁺) Self-assembling with cucurbituril to form 2:1 host-guest compound, and performing photoreduction, electroreduction, chemical reduction and other methods to obtain MPT²⁺Reduction to form radical cation MPT^·+Further constructing supramolecular free radical dimer 2MPT^·+CB, 2MPT due to host enhanced charge transfer interactions^·+the-CB has stronger NIR-II absorption, thereby realizing higher photothermal conversion efficiency. Unfortunately, the preparation process is complicated, the cost is high, and the preparation method is not suitable for large-scale preparation. Wang and his research group synthesized a narrow bandgap donor-acceptor conjugated polymer with enhanced light-to-heat conversion efficiency using a thiophene fused benzodifurandione based oligomer (p-phenyleneyl) as the acceptor moiety and 2, 2' -bithiophene as the donor moiety. However, the high cost and complexity of synthesizing such materials limits their further applications.

Disclosure of Invention

In order to overcome the defects of the prior art, the invention provides the organic NIR-II photothermal conversion film and the preparation method and application thereof, the preparation method is simple, the cost is low, the large-scale production can be realized, the prepared organic NIR-II photothermal conversion film has good uniformity and stable property, the NIR-II photothermal conversion efficiency is excellent, and the initial heating rate is as high as 30 ℃/s.

The technical solution of the invention is realized by the following technical scheme:

the invention provides an organic NIR-II photothermal conversion film which is a hydrogen bond aggregate formed by hydrogen bond interaction between 3,3 ', 5, 5' -tetramethylbenzidine oxide and agarose.

The second aspect of the present invention provides a method for preparing the above organic NIR-II photothermal conversion film, comprising the steps of:

1) carrying out oxidation reaction on the 3,3 ', 5, 5' -tetramethylbenzidine mother solution under the catalysis of the nano-enzyme and in the presence of a buffer solution to obtain a nano-enzyme/3, 3 ', 5, 5' -tetramethylbenzidine oxide composite solution;

selecting a nano enzyme with oxidase-like property such as CoPt @ G for catalyzing oxidation of 3,3 ', 5, 5' -tetramethylbenzidine (TMB, structural formula shown in figure 1a) to generate 3,3 ', 5, 5' -tetramethylbenzidine oxide (oxTMB, prepared from TMB and its dicationic structure TMB⁺⁺The structural formula of the formed charge transfer compound is shown in figure 1b), and the CoPt @ G has strong and stable catalytic activity, so that the catalytic activity is unchanged after acidic and high-temperature treatment, and the mutual conversion between TMB and oxTMB ensures that the CoPt @ G/TMB system can realize the cycle phenomena of color development-color fading-color development under the weak acidic condition through temperature control.

2) Mixing the nano enzyme/3, 3 ', 5, 5' -tetramethyl benzidine oxide composite solution obtained in the step 1) with agarose and heating to obtain sol;

3) preparing a film from the sol obtained in the step 2):

31) cooling the sol to obtain a first hydrogel;

32) continuously carrying out catalytic oxidation reaction on the first hydrogel to obtain a second hydrogel;

33) and drying the second hydrogel to obtain the organic NIR-II photo-thermal conversion film.

The organic NIR-II photothermal conversion film is mainly formed by H-aggregates (figure 1d) due to the interaction (hydrogen bond) between the oxTMB and the agarose molecules (figure 1c), has extremely high photothermal conversion efficiency, and is applied to a 1064nm laser (1W/cm)²) Under irradiation, a rise of 130 ℃ can be achieved for a decade or so.

Preferably, step 1) further comprises at least one of the following technical features:

11) the 3,3 ', 5, 5' -tetramethyl benzidine mother liquor comprises 3,3 ', 5, 5' -tetramethyl benzidine and an organic solvent;

12) the concentration of the 3,3 ', 5, 5' -tetramethyl benzidine in the 3,3 ', 5, 5' -tetramethyl benzidine mother liquor is 5-20 mmol/L, such as 5-10 mmol/L or 10-20 mmol/L;

13) the concentration of the 3,3 ', 5, 5' -tetramethyl benzidine is 0.01-0.04 mmol/L based on the total volume of the 3,3 ', 5, 5' -tetramethyl benzidine mother liquor and the buffer solution;

14) the nano enzyme is a composite nano material wrapped by graphene, and the composite nano material is a core-shell structure formed by taking the graphene as a shell and taking a cobalt-platinum alloy as a core;

15) the mass ratio of the 3,3 ', 5, 5' -tetramethyl benzidine to the nano enzyme is 0.24024: 1-0.96136: 1;

16) the buffer solution is at least one selected from a phosphate buffer solution, an acetate buffer solution and a carbonate buffer solution;

17) the pH of the buffer solution is 3.5-5.5, such as 3.5-5 or 5-5.5;

18) the temperature of the catalytic oxidation reaction is 16-25 ℃.

More preferably, at least one of the following technical characteristics is also included:

111) in feature 11), the organic solvent is selected from at least one of ethanol and dimethyl sulfoxide;

141) the characteristic 14) is that the particle size of the composite nano material is 5-7 nm;

142) in the characteristic 14), the number of graphene layers on the surface of the cobalt-platinum alloy is 3-4

143) The characteristic 14) is that the molar ratio of cobalt to platinum in the cobalt-platinum alloy is 1: 1.5-1: 2.

The nano enzyme is obtained by a preparation method comprising the following steps:

a) mixing SiO₂Adding the mixture into a methanol solution for ultrasonic treatment for 1-2 hours to obtain a solution A, wherein SiO is₂The mass-to-volume ratio of the methanol to the methanol is 1: 150-200, the mass unit is g, and the volume unit is mL; mixing Co (NO)₃)₂·6H₂O and 5-20 mg/mL H₂PtCl₆Mixing the solutions to obtain a solution B, and mixing 30-40 parts by volume of the solution BMixing the solution A and 1 volume part of the solution B, performing ultrasonic treatment for 1-2 hours, removing methanol, and drying the obtained mixture.

b) Grinding the dried mixture of step a) into powder and then mixing with CH₄The flow rate is 120-150 cm³Igniting for 5-7 min under the condition of/mL airflow, wherein the ignition temperature is 900-1000 ℃, cooling, mixing with an HF solution, and then treating the solid in the solution, namely the graphene-coated CoPt composite nano-particles.

Preferably, the power of the ultrasonic treatment in the step a) is 170-200 w.

Preferably, in the step a), the molar ratio of cobalt to platinum in the solution B is 1: 1.5-1: 2.

Preferably, in the step b), the mass-to-volume ratio of the powder to the HF solution is 0.75-0.85: 25-30, the mass unit is g, the volume unit is mL, and the mass fraction of the HF solution is more than or equal to 40.0%.

Preferably, step 2) further comprises at least one of the following technical features:

21) the mass ratio of 3,3 ', 5, 5' -tetramethylbenzidine to the agarose is 0.00072: 1-0.00288: 1;

22) the mass ratio of the agarose to the nano enzyme/3, 3 ', 5, 5' -tetramethylbenzidine oxide composite solution obtained in the step 1) is 1: 100-3: 100, such as 1: 100-2: 100 or 2: 100-3: 100, respectively;

23) the heating temperature is 90-120 deg.C, such as 90-100 deg.C or 100-120 deg.C.

Preferably, in step 31), the cooling temperature is 10-25 ℃, such as 10-20 ℃ or 20-25 ℃.

Preferably, in the step 32), the temperature of the catalytic oxidation reaction is 16-25 ℃, such as 16-20 ℃ or 20-25 ℃.

Preferably, in step 33), the drying temperature is 16-25 ℃, such as 16-20 ℃ or 20-25 ℃.

Preferably, in step 33), the drying humidity is 20-30%, such as 20-25% or 25-30%.

The third aspect of the invention provides the application of the organic NIR-II photothermal conversion film in tumor photothermal treatment materials.

Compared with the prior art, the invention has at least one of the following beneficial effects:

a) the preparation method is simple, low in cost and suitable for large-scale production.

b) The organic NIR-II photo-thermal conversion film has good uniformity, stable property and excellent NIR-II photo-thermal conversion efficiency, the initial heating rate can be as high as 30 ℃/s, and the initial heating rate is incomparable in organic photo-thermal materials.

c) The invention selects stable nano enzyme to realize the re-catalysis in the hydrogel.

d) The invention adopts agarose with good biocompatibility and low price as a substrate material, helps 3,3 ', 5, 5' -tetramethylbenzidine oxide, namely oxTMB, to form H-aggregates (hydrogen bond aggregates) structurally, and enables the material to be more stable, so that the material has good application value in various fields.

Drawings

FIG. 1 shows the structural formula of the raw material used in the present invention.

Wherein, a) is TMB structural formula;

b) is of the structural formula of oxTMB;

c) is a linear agarose structure formula;

d) is a structural formula of H-aggregate formed by the interaction (hydrogen bond) between the oxTMB and the agarose molecule.

FIG. 2 is a representation diagram of an organic NIR-II photothermal conversion film prepared by the invention, namely a CTAG composite film.

Wherein a) is an ultraviolet absorption spectrogram of the oxTMB in different states;

b) is a Raman spectrogram of the oxTMB in the solution and the membrane;

c) the interaction of oxTMB with agarose at different concentrations is plotted.

Fig. 3 is a picture of different films prepared in the examples.

Wherein, a) is a flow chart for preparing a CTAG composite membrane;

b) bright field plots of films prepared for different film substrates;

c) uv absorption spectra of films prepared for different film substrates;

d) optical micrographs of membranes prepared for different drying conditions.

Fig. 4 is a graph of the photothermal properties of the films prepared in the examples.

Wherein a) is a near-infrared imaging diagram of CTAG composite membrane photothermal temperature rise;

b) photo-thermal temperature rise curve chart of the four films;

c) temperature rise curve diagrams of the CTAG composite membrane under different laser powers;

d) and (3) a long-term photo-thermal stability performance diagram of the CTAG composite membrane.

Fig. 5 is a biocompatibility map of the membrane prepared in example 1.

Wherein, a) is the cytotoxicity diagram of CAG and CTAG membranes on fibroblasts;

b) is a statistical graph of the body weight of the mice in which the membranes are in the mice for 30 days;

c) h & E staining pattern of organs and skin of mice 30 days after membrane implantation.

Fig. 6 is a graph of the therapeutic effect of the membrane prepared in example 1.

Wherein, a) is the near infrared thermal image of the membrane in the body of a mouse;

b) the photothermal temperature curve of the membrane in the body of a mouse is shown;

c) bright field pictures of tumor-implanted mice before and after photothermal therapy are obtained;

d) body weight change plots within ten days after treatment of the mice;

e) a graph of tumor volume change after treatment of mice;

f) tumor brightfield patterns ten days after treatment for mice.

FIG. 7 is a graph showing the effect of drying temperature (16 ℃, 20 ℃, 25 ℃) and relative humidity of drying (20% RH, 25% RH, 30% RH) on the photothermal effect of the formed film.

Detailed Description

The technical solution of the present invention is illustrated by specific examples below. It is to be understood that one or more method steps mentioned in the present invention do not exclude that further method steps may be present before or after the combination step or that further method steps may be inserted between the explicitly mentioned steps; it should also be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Moreover, unless otherwise indicated, the numbering of the various method steps is merely a convenient tool for identifying the various method steps, and is not intended to limit the order in which the method steps are arranged or the scope of the invention in which the invention may be practiced, nor to change or adjust their relative relationship, without materially changing the technical details, but rather considering the scope of the invention in which the invention may be practiced.

Example 1

The preparation method of the CoPt @ G/TMB agarose composite membrane material comprises the following steps:

(1) preparing 25mM Phosphate Buffer Solution (PBS) with pH 5 by using sodium dihydrogen phosphate and disodium hydrogen phosphate;

preparing 10mM TMB mother liquor by using ethanol as a solvent, and storing at 4 ℃;

the treated and quantified CoPt @ G nanoparticles were diluted to 500. mu.g/mL.

The CoPt @ G nano-particle is a nano-enzyme catalyst and is a composite nano-material wrapped by graphene, the composite nano-material is of a core-shell structure formed by taking graphene as a shell and taking a cobalt-platinum alloy as a core, the particle size of the composite nano-material is 5-7 nm, the number of graphene layers on the surface of the cobalt-platinum alloy is 3-4, the molar ratio of cobalt to platinum in the cobalt-platinum alloy is 1:1.5, and the preparation method comprises the following steps:

a) mixing SiO₂Adding into methanol solution, and performing ultrasonic treatment for 2 hr to obtain solution A, wherein SiO is₂The mass-to-volume ratio of the methanol to the methanol is 1: 200, the mass unit is g, and the volume unit is mL; mixing Co (NO)₃)₂·6H₂O and 20mg/mL H₂PtCl₆Mixing the solutions to obtain a solution B, mixing 40 parts by volume of the solution A and 1 part by volume of the solution B, carrying out ultrasonic treatment for 1h at the power of 200w, removing methanol, and drying the obtained mixture. Preferably, the first and second electrodes are formed of a metal,

b) grinding the dried mixture of step a) into powder and then mixing with CH₄The flow rate is 120cm³Igniting for 7min under the condition of gas flow of/mL, wherein the ignition temperature is 1000 ℃, cooling, mixing with HF solution, and then treating the solid in the solution to obtain the productThe graphene-coated CoPt composite nanoparticles comprise CoPt composite nanoparticles, wherein the mass-to-volume ratio of powder to HF solution is 0.85:30, the mass unit is g, the volume unit is mL, and the mass fraction of the HF solution is 40.0%.

Adding 48.5mL of PBS with pH value of 5 into a 200mL beaker, adding 1mL of 10mM TMB mother liquor and 0.5mL of 500 mu G/mL CoPt @ G, uniformly stirring in an air environment at 20 ℃, and gradually changing the solution from colorless to blue to obtain a CoPt @ G/TMB blue composite solution A; adding weighed 0.5g of agarose powder (namely, the concentration of agarose is 1 percent, and the concentration is the mass of agarose/the mass of the blue composite solution A is 100 percent) into the solution A, and uniformly mixing to obtain a solution B; heating the solution B in a microwave oven at 100 ℃ for 80 seconds, and taking out the heated solution after heating to obtain faded sol C; when the C sol is hot, 3mL of the C sol is sucked into a dish cover of a small cell culture dish by a pipette gun and cooled in an air environment at 20 ℃, gel D is formed within a few minutes, and the color of the gel is slightly restored to light blue. Note that the removal of the sol from the beaker is fast, otherwise the C sol cools directly in the beaker to form a gel.

(2) And (2) putting the D gel prepared in the step (1) in an air environment at the temperature of 20 ℃ for continuous catalytic reaction, gradually changing the color of the D gel to blue, and changing the D gel to deep blue after 24 hours, wherein the weight loss rate is about 45%. And drying the mixture for 24 hours at the temperature of 16 ℃ and the humidity of 30 percent, wherein the hydrogel is lighter and lighter, the color is blue all the time, until the weight loss rate reaches a critical value, the blue color is changed into purple in a short time (about 0.5 hour), after the blue color fully forms a uniform purple film, the weight loss rate reaches about 98.5 percent, and the purple film naturally falls off from the dish cover, so that the purple film with the weight of about 0.03g, the thickness of about 32 mu m and smooth and wrinkle-free surface is obtained. The whole membrane preparation process can be seen in FIG. 3a), and simultaneously, a blank agarose membrane (AG film), a TMB agarose membrane (TAG film), a CoPt @ G agarose membrane (CAG film) are prepared according to the above steps.

As can be seen from FIG. 2a, the UV absorption spectra of oxTMB are different in the solution (i.e., blue complex solution A), the hydrogel (i.e., the hydrogel obtained before drying for 24 hours at 30% humidity at 16 ℃) and the film (i.e., the violet film obtained after drying), with the degree of blue shift in the hydrogel being not large relative to the solution, and the degree of blue shift in the film being large relative to the solution, indicating that oxTMB is gradually H-aggregated. As can be seen from FIG. 2b, the Raman spectra of the solution and the membrane are almost consistent, which proves that the blue substance in the solution is the same as the purple substance in the membrane, and the blue substance may be accumulated in different ways, and the purple of the CTAG composite membrane is H-aggregation derived from oxTMB by combining with the ultraviolet absorption spectrum.

The CTAG composite film prepared by the invention has excellent photo-thermal efficiency, and as shown in figure 4a, the composite film is irradiated by laser with the wavelength of 1064nm (the laser power density is 1.0W/cm)²) The temperature can be rapidly raised from 25 ℃ to 160 ℃ within 14 seconds, and the initial temperature raising rate can even reach 30 ℃/s. To eliminate such high efficiency photothermal conversion by CoPt @ G, we compared AG film, TAG film, CAG film and CTAG film (AG film is agarose film; TAG film is TMB agarose film; CAG film is CoPt @ G agarose film; CTAG film is CoPt @ G/TMB agarose film) at 0.5W/cm²The effect of temperature increase under 1064nm laser irradiation, and only the CTAG film had an excellent effect of temperature increase in FIG. 4 b. The photothermal effect of the CTAG film is also related to the laser power, and the higher the power, the higher the temperature rise (fig. 4 c). Finally, we investigated the long-term photothermal stability of the CTAG membrane, and performed photothermal conversion test on the same membrane four times in one month (fig. 4d), and the results prove that the membrane has excellent stability and has great potential to be applied to the clinical field.

Biocompatibility in vitro and in vivo

The CTAG membranes (CoPt @ G/TMB agarose membranes) obtained by the above preparation were potentially cytotoxic to normal cells, and each membrane was incubated with the same number of C3H/10T1/2 (mouse embryonic fibroblasts) normal cells for 1, 3, and 5 days, and the relative survival rate of C3H/10T1/2 cells was determined by the cck-8 method. As shown in FIG. 5a, the co-incubation of CAG with CTAG membrane did not cause cytotoxicity compared to the control without any treatment, indicating that neither the incorporation of trace CoPt @ G nor the formation of oxTMB affected the biocompatibility of the agarose membrane.

To further assess the potential toxicity of CTAG membranes in vivo, both CAG and CTAG membranes were studied systemically after subcutaneous implantation in female Balb/c mice. Since degradation of agarose may lead to the release of CoPt @ G and oxTMB, long-term toxicity studies of CAG and CTAG membranes are necessary. Carefully monitoring mice implanted with CAG and CTAG membranes, no mortality was observed within 30 days and no apparent toxicity was seen by body weight recordings (figure 5 b). After 30 days of implantation, mice were sacrificed, and heart, liver, spleen, lung, kidney and skin wounds were sectioned and H & E stained for tissue analysis. As shown in fig. 5c, no injury or inflammatory lesion is seen in each organ, and histopathological abnormalities or lesions in both groups are negligible, which indicates that CAG and CTAG membranes can be well applied to the body.

In vivo photothermal cancer treatment

The in vivo photothermal treatment effect is verified by the excellent biocompatibility and the ultra-efficient photothermal conversion of the CTAG film. 4T1 tumor-bearing mice were randomly divided into 6 groups, including group 1: control, group 2: control + laser, group 3: CAG film, group 4: CAG film + laser, group 5: CTAG film, group 6: CTAG film + laser, where CTAG film is the CTAG film obtained in the above preparation (CoPt @ G/TMB agarose film). The skin at the margins of the mouse tumor was scarred, covered with CAG or CTAG film on the tumor surface, laser irradiated at 1064nm for ten minutes, and treated with conventional wound sutures and antibiotics. By comparison, wounds were not treated with any membrane but were also sutured open as a control. Real-time temperature and in situ thermal images of the tumor area were recorded with an infrared photothermal camera. Under 1064nm laser irradiation, the temperature of the tumor site using the CTAG membrane was sharply increased from 33 ℃ to 52 ℃ within the initial 20 seconds and maintained at 60 ℃ for 10 minutes, whereas the tumor temperature increase was negligible in mice using the CAG membrane and the control group (FIGS. 6a, b). The body weight and tumor volume of mice of all groups were monitored every two days. There was no apparent fluctuation in body weight of mice in all groups (fig. 6d), indicating that treatment in each group had little adverse effect on the health of the mice. More importantly, tumors of the CTAG + Laser group gradually disappeared without recurrence, and the original wound healed within 10 days (fig. 6 c). After six groups of mice are treated for 10 days, the weights and photographs of tumors are shown in fig. 6e and f, the group with the minimum average tumor is a CTAG + Laser group, and the CTAG membrane is further confirmed to be capable of effectively inhibiting the tumor growth under the irradiation of near-infrared Laser.

Example 2

The experimental procedure was the same as in example 1, except that the influence of the drying conditions (temperature: 16 ℃,30 ℃,45 ℃,60 ℃; humidity: 30% RH, 90% RH) on the structure of the formed CTAG membrane was examined, and it was found from the experimental results (fig. 3d) that the influence on the structure of the formed CTAG membrane was large in the examined temperature and humidity ranges, the temperature was high and humidity was low, the drying speed was fast, and the oxTMB almost completely formed aggregates; the temperature is high, the humidity is high, the drying speed is low, and the oxTMB can be decomposed at high temperature for a long time and cannot form an aggregate film; the temperature is low, the humidity is low, the drying speed is slightly slow, but a uniform high-quality aggregate film can be formed; since the temperature is low and the humidity is high, and the drying speed is very slow, the oxTMB is precipitated to form oxTMB crystals, which is not favorable for forming aggregates. Finally preferred drying conditions are low temperature and low humidity, i.e. (16 ℃, 30% humidity).

Example 3

The procedure was carried out as in example 1, except that the effect of different film-forming substrates on the aggregates formed, including sodium alginate and gelatin, was examined. From the experimental results (fig. 3b, c), the composite membrane prepared from gelatin is blue, and the absorption peak is not blue-shifted, i.e. no oxTMB H-aggregate is formed; the middle part of the frontal complex membrane prepared by sodium alginate is light purple, the edge is dark blue, the obvious coffee ring phenomenon is caused, and the absorption peak at 652nm is blue-shifted to 599nm, namely, a small degree of H-aggregation is formed; the whole membrane of the composite membrane prepared from the agarose has uniform color, is purple and transparent, and has large H-aggregation degree when the absorption peak at 652nm is blue-shifted to 556 nm. Therefore, we speculate that such interactions as hydrogen bonding may exist between oxTMB and agarose linear molecules (FIG. 1 d). Finally, agarose is preferred as the film-forming substrate of the present invention.

Example 4

The procedure was carried out as in example 1, with the difference that the effect of different agarose concentrations (0.2%, 0.5%, 0.7%, 1.0%, 2.0% and 3.0%) on the film-forming structure was investigated. From the experimental results (FIG. 2c), we found that the larger the agarose concentration, the larger the blue shift of the absorption peak at 652nm, and that there was a clear interaction between oxTMB and agarose molecules after the formation of hydrogel. The lower the agarose concentration, the more easily oxTMB crystals are formed because of the weak interaction between the two; when the concentration of the agarose reaches 1.0 percent, the precipitation of crystals can be avoided, and the membrane of the high-purity oxTMB H-aggregate is obtained; considering that the photothermal conversion effect of the composite membrane prepared at an agarose concentration of 1.0 to 3.0% is excellent, 1.0 to 3.0% agarose is preferable as the mass fraction of the membrane used in the present invention. Note: agarose concentration-the mass of agarose/the mass of blue complex solution a-100%.

Example 5

The procedure was the same as in example 1, except that the effect of the drying temperature (16 ℃, 20 ℃, 25 ℃) on the photothermal effect of the formed film was examined, and it was found from the experimental results (fig. 7a) that the effect on the photothermal performance of the formed film was not significant in the examined drying temperature range (16 to 25 ℃) when the relative humidity was 30%, and the most preferable drying temperature was 16 ℃.

Example 6

The procedure was the same as in example 1, except that the effect of the relative humidity of drying (20% RH, 25% RH, 30% RH) on the photothermal effect of the formed film was examined, and it was found from the experimental results (fig. 7b) that the effect on the photothermal performance of the formed film was not large in the relative humidity range (20% RH to 30% RH) examined when the drying temperature was 16 ℃.

While the invention has been described with respect to a preferred embodiment, it will be understood by those skilled in the art that the foregoing and other changes, omissions and deviations in the form and detail thereof may be made without departing from the scope of this invention. Those skilled in the art can make various changes, modifications and alterations without departing from the spirit and scope of the present invention, and all equivalent changes, modifications and alterations to the present invention are equivalent embodiments of the present invention; meanwhile, any changes, modifications and variations of the above-described embodiments, which are equivalent to those of the technical spirit of the present invention, are within the scope of the technical solution of the present invention.

Claims

1. An organic NIR-II photothermal conversion film is characterized in that hydrogen bond aggregates are formed by hydrogen bond interaction between 3,3 ', 5, 5' -tetramethylbenzidine oxide and agarose; the 3,3 ', 5, 5' -tetramethylbenzidine oxide is prepared by oxidation reaction of 3,3 ', 5, 5' -tetramethylbenzidine mother liquor under the action of nano enzyme and in the presence of buffer; the nano enzyme is a composite nano material wrapped by graphene, and the composite nano material is a core-shell structure formed by taking graphene as a shell and taking a cobalt-platinum alloy as a core.

2. The method of making an organic NIR-II photothermal conversion film according to claim 1, comprising the steps of:

1) carrying out oxidation reaction on the 3,3 ', 5, 5' -tetramethylbenzidine mother solution under the catalysis of nano enzyme and in the presence of buffer solution to obtain a nano enzyme/3, 3 ', 5, 5' -tetramethylbenzidine oxide composite solution; the nano enzyme is a composite nano material wrapped by graphene, and the composite nano material is a core-shell structure formed by taking the graphene as a shell and taking a cobalt-platinum alloy as a core;

3) preparing a film from the sol obtained in the step 2):

31) cooling the sol to obtain a first hydrogel;

3. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in step 1), the 3,3 ', 5, 5' -tetramethylbenzidine mother liquor comprises 3,3 ', 5, 5' -tetramethylbenzidine and an organic solvent.

4. The method for preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in step 1), the concentration of 3,3 ', 5, 5' -tetramethylbenzidine in the 3,3 ', 5, 5' -tetramethylbenzidine mother liquor is 5 to 20 mmol/L.

5. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in step 1), the concentration of 3,3 ', 5, 5' -tetramethylbenzidine is 0.01 to 0.04mmol/L based on the total volume of the 3,3 ', 5, 5' -tetramethylbenzidine mother liquor and the buffer.

6. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein, in step 1), the mass ratio of 3,3 ', 5, 5' -tetramethylbenzidine to the nanoenzyme is 0.24024: 1-0.96136: 1.

7. the method for preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in step 1), the buffer is at least one selected from the group consisting of a phosphate buffer, an acetate buffer and a carbonate buffer.

8. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in step 1), the pH of the buffer solution is 3.5 to 5.5.

9. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein the reaction temperature of the oxidation reaction in step 1) is 16 to 25 ℃.

10. The method of preparing an organic NIR-II photothermal conversion film according to claim 3, wherein the organic solvent is at least one selected from the group consisting of ethanol and dimethylsulfoxide.

11. The method of claim 2, wherein the particle size of the composite nanomaterial is 5 to 7 nm.

12. The method of claim 2, wherein the number of graphene layers on the surface of the cobalt-platinum alloy is 3-4.

13. The method of claim 2, wherein the molar ratio of cobalt to platinum in the cobalt-platinum alloy is 1:1.5 to 1: 2.

14. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein, in step 2), the mass ratio of 3,3 ', 5, 5' -tetramethylbenzidine to the agarose is 0.00072: 1-0.00288: 1.

15. the method for preparing an organic NIR-II photothermal conversion membrane according to claim 2, wherein the mass ratio of agarose to nanoenzyme/3, 3 ', 5, 5' -tetramethylbenzidine oxide composite solution obtained in step 1) in step 2) is 1: 100-3: 100.

16. the method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein the heating temperature in step 2) is 90 to 120 ℃.

17. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein the cooling temperature in step 31) is 10 to 25 ℃.

18. The method for preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in the step 32), the catalytic oxidation reaction temperature is 16 to 25 ℃.

19. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein the drying temperature in step 33) is 16 to 25 ℃.

20. The method of preparing an organic NIR-II photothermal conversion film according to claim 2, wherein in the step 33), the drying humidity is 20 to 30%.

21. Use of the organic NIR-ii photothermal conversion film according to claim 1 for the preparation of tumor photothermal therapy material.