Active oxygen activated near-infrared region photo-thermal reagent as well as preparation method and application thereof

Abstract

The invention discloses an active oxygen activated near-infrared region photo-thermal reagent and a preparation method and application thereof.The near-infrared region photo-thermal reagent with active oxygen response is constructed by means of etherification reaction of phenolic hydroxyl functionalized aza-BODIPY dye and p-bromophenylboronic acid pinacol ester and further prepared into nanoparticles, and the near-infrared region photo-thermal reagent with the active oxygen response function is prepared into the active oxygen activated near-infrared region photo-thermal reagent. After the nano particle reacts with active oxygen, the photo-thermal efficiency of the nano particle is remarkably improved under 808nm laser illumination, and the nano particle has an excellent photo-thermal imaging effect and a photo-thermal treatment function.

Description

Technical Field

[0001] The present invention belongs to the technical field of photothermal reagents, and specifically relates to an active oxygen activated near-infrared photothermal reagent and a preparation method and application thereof. Background Art

[0002] Photothermal therapy (PTT) is a non-invasive tumor treatment method that converts near-infrared light (NIR) into local high temperature through photothermal reagents to selectively kill tumor cells. Compared with traditional therapies, PTT has the advantages of strong spatial controllability and few side effects. However, existing organic photothermal reagents such as polypyrrole and indocyanine green generally have the problem of insufficient targeting. After systemic administration, they are easily accumulated in normal tissues, causing nonspecific thermal damage. In addition, some inorganic nanomaterials, such as gold nanorods, have high photothermal conversion efficiency, but the biological toxicity caused by long-term retention limits their clinical application. Therefore, it is crucial to develop "smart" organic photothermal reagents with the ability to respond to the lesion microenvironment.

[0003] Designing intelligent nanodiagnostic and therapeutic systems that are responsive to the tumor microenvironment is of great significance. Among them, hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) overexpressed in the tumor microenvironment, with a concentration (50–100 μM) significantly higher than that in normal tissue (<20 μM), making it an ideal pathological marker.

[0004] In recent years, H2O2-responsive probes have made some progress in the fields of drug delivery and imaging, but their application in photothermal therapy still faces challenges: on the one hand, most H2O2-activated materials rely on chemical bond breaking or structural rearrangement to achieve functional switching, with slow response kinetics, making it difficult to accurately match the therapeutic time window; on the other hand, the light absorption of existing systems is mostly concentrated in the ultraviolet-visible light region (<700nm), and the tissue penetration depth is limited, which restricts their further clinical application.

[0005] Currently, a few studies have attempted to introduce H2O2-responsive groups (such as boronates and thioethers) into organic conjugated molecular backbones, but the contrast between their photothermal properties before and after activation is low (<30%) and they lack precise control of NIR absorption. Furthermore, the biocompatibility and metabolic pathways of these agents have not been systematically evaluated, limiting their potential for clinical translation.

[0006] Therefore, there is an urgent need to develop an organic photothermal agent with high H2O2 response sensitivity, efficient NIR photothermal conversion and good biosafety to achieve precise tumor ablation and reduce systemic toxicity. Summary of the Invention

[0007] To solve the above technical problems, the present invention provides a reactive oxygen-activated near-infrared photothermal reagent, a preparation method, and an application thereof. After the photothermal reagent is prepared into nanoparticles, it has excellent photothermal imaging effects and photothermal therapy functions under the activation of reactive oxygen.

[0008] The technical solution adopted by the present invention is as follows:

[0009] The present invention provides an active oxygen-activated near-infrared photothermal reagent, the structural formula of the active oxygen-activated near-infrared photothermal reagent is:

[0010]

[0011] The present invention also provides a method for preparing the active oxygen activated near-infrared region photothermal reagent, the preparation method comprising the following steps: 2Cl OH-OBDP is mixed with 4-bromomethylphenylboronic acid pinacol ester and an inorganic base, and an organic solvent is added under an inert atmosphere. The mixture is reacted at 55-65°C for 6-12 hours, and then post-treated to obtain an active oxygen-activated near-infrared photothermal reagent.

[0012] described 2Cl The structural formula of OH-OBDP is:

[0013] Furthermore, 2Cl The molar ratio of OH-OBDP, 4-bromomethylphenylboronic acid pinacol ester and inorganic base is 1:2-3:2-3, preferably 1:3:3.

[0014] The inorganic base is one of potassium carbonate and sodium carbonate.

[0015] The inert gas is nitrogen.

[0016] The organic solvent is anhydrous acetonitrile.

[0017] 2Cl The concentration of OH-OBDP in the organic solvent is 0.01 to 0.05M, preferably 0.01 to 0.02M.

[0018] The post-treatment method comprises: filtering the reaction solution, collecting the filtrate and performing extraction, concentrating the organic phase collected by the extraction, and then performing column chromatography.

[0019] Furthermore, the eluent used in the column chromatography is a mixed solvent consisting of petroleum ether and dichloromethane in a volume ratio of 1:1.

[0020] The present invention also provides active oxygen-activated near-infrared photothermal reagent nanoparticles, which are prepared by the following method: dissolving the active oxygen-activated near-infrared photothermal reagent described in the present invention in an organic solvent miscible with water, then adding it to water containing a surfactant under high-speed stirring, and then dialyzing it.

[0021] The water-miscible organic solvent is any one or more of dioxane, dimethyl sulfoxide, and N,N-dimethylformamide.

[0022] The surfactant is DSPE-PEG 2000 , Tween 80, or F127.

[0023] The dialysis was performed using a dialysis bag with a molecular weight cut-off of 3500 Da for 24 h.

[0024] The volume ratio of the organic solvent to water is 1:5 to 15, preferably 1:10.

[0025] The mass ratio of the active oxygen activated near-infrared photothermal agent to the surfactant is 1:1 to 5, preferably 1:2.

[0026] The present invention also provides the use of the reactive oxygen species activated near-infrared region photothermal agent nanoparticles in the preparation of tumor photothermal imaging agents or tumor photothermal treatment agents.

[0027] The present invention constructs a near-infrared photothermal reagent with active oxygen response by reacting a phenolic hydroxyl functionalized aza-fluoroboron fluorescent dye with 4-bromophenylboronic acid pinacol ester through an etherification reaction. The preparation method is simple and can be completed in a single step. The active oxygen response principle is as follows: when the probe is in the presence of H2O2, the phenylboronic acid ester will be removed, and then a 1,6-elimination reaction will occur to release the phenolic hydroxyl group. Under physiological conditions, the phenolic hydroxyl group exists in the form of phenol anion, and a new absorption peak will be generated at 780nm. Therefore, its light absorption capacity is significantly enhanced under 808nm laser light, resulting in a significantly enhanced photothermal effect after H2O2 triggering activation, such as Figure 2 After being prepared into nanoparticles, the nanoparticles react with active oxygen and have excellent photothermal imaging effects and photothermal therapy functions.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] After the active oxygen-activated near-infrared photothermal reagent provided by the present invention is prepared into nanoparticles, its ultraviolet-visible-near-infrared absorption spectrum undergoes a significant red shift after the addition of active oxygen H2O2. After reacting with H2O2, its photothermal conversion efficiency increases from 17.4% to 35.5% under 808nm light.

[0030] The reactive oxygen species activated near-infrared region photothermal reagent nanoparticles provided by the present invention can realize photothermal imaging of tumor tissues and have a very excellent photothermal tumor inhibition effect under 808nm light. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The synthetic route of ROS-OBDP;

[0032] Figure 2 Schematic diagram of the reaction between ROS-OBDP and H2O2;

[0033] Figure 3 is the H NMR spectrum of ROS-OBDP;

[0034] Figure 4 It is the high-resolution mass spectrum of ROS-OBDP;

[0035] Figure 5 DLS results (a) and TEM results (b) of ROS-OBDP nanoparticles prepared in Example 2;

[0036] Figure 6 (a) Changes in the UV-visible-near-infrared absorption spectra of ROS-OBDP nanoparticles after incubation with different concentrations of H2O2; (b) The linear relationship between the ratio of the absorption wavelengths at 775 nm to 715 nm and the H2O2 concentration;

[0037] Figure 7 (a) UV-Vis-NIR spectra of ROS-OBDP nanoprobes after incubation with H2O2 in PBS buffer (pH 7.4) for different time periods; (b) λ 775nm The change of the ratio of the wavelength at λ / λ715 nm over time; (c) The change of the fluorescence emission spectrum of the ROS-OBDP nanoprobe after incubation with H2O2 in PBS buffer over time; (d) The normalized fluorescence intensity of the ROS-OBDP nanoprobe at 912 nm after incubation with other substances in PBS buffer for 24 hours;

[0038] Figure 8(a) Temperature rise / fall curves of pure water, untreated, and H2O2-pretreated ROS-OBDP nanoprobes recorded during 808 nm laser irradiation for 1800 seconds; (b) Infrared thermal imaging images of pure water, untreated, and H2O2-treated ROS-OBDP nanoprobes after 808 nm laser irradiation for 10 minutes; (c) Linear fitting curve obtained based on the relationship between lnθ and time during the cooling process; (d) Concentration-dependent temperature rise curves of H2O2-pretreated ROS-OBDP nanoprobes when irradiated with 808 nm laser at different concentrations; (e) Comparison of the photothermal stability of H2O2-pretreated ROS-OBDP nanoprobes and ICG during 5 heating-cooling cycles; (f) Ultraviolet-visible-near-infrared (UV-Vis-NIR) absorption spectra of H2O2-pretreated ROS-OBDP nanoprobes before and after 5 heating-cooling cycles;

[0039] Figure 9 The photothermal curves before and after the reaction of ROS-OBDP nanoparticles with H2O2 and the corresponding relationship between -lnθ and illumination time;

[0040] Figure 10 Photothermal effect of ROS-OBDP nanoparticles in 4T1 tumor-bearing mice after 808 nm light irradiation, with the laser alone group serving as the control group;

[0041] Figure 11 (a) Changes in tumor volume in different experimental groups; (b) Macroscopic photographs of tumor tissues taken from each group after treatment; (c) Average tumor mass of each group after treatment; (d) Changes in mouse body weight during the entire treatment process. DETAILED DESCRIPTION

[0042] The present invention is described in detail below with reference to the embodiments.

[0043] All PBS solutions of substances in this article were obtained by dispersing the substances into PBS buffer solution with pH 7.4.

[0044] 2Cl The preparation method of OH-OBDP refers to Example 5 disclosed in Chinese Patent 2024119890761, and the preparation route is as follows:

[0045]

[0046] The specific preparation process is as follows:

[0047] Synthesis of Compound A5: p-Anisaldehyde (2.72 g, 20 mmol, 1.0 equiv.) and 1-(4-(propyleneoxy)-3,5-dichlorophenyl)ethane-1-one (4.88 g, 20 mmol, 1.0 equiv.) were dissolved in 20 ml of ethanol, and sodium hydroxide (800 mg, 20 mmol, 1.0 equiv.) was added thereto. The mixture was reacted at room temperature overnight, and the solid product A5 was obtained by filtration.

[0048] Synthesis of compound B5: A5 (4.5 g, 12.4 mmol, 1.0 equiv.) was dissolved in 20 ml of ethanol, and nitromethane (7.56 g, 124 mmol, 10 equiv.) and sodium hydroxide (496 mg, 12.4 mmol, 1.0 equiv.) were added. The mixture was reacted at 70°C for 12 h. The ethanol was dried and extracted with dichloromethane and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then subjected to column chromatography using a 1:1 volume ratio of dichloromethane to petroleum ether as the eluent to obtain product B5.

[0049] Synthesis of compound C5: Compound B5 (3.0 g, 7.1 mmol, 1.0 equiv.) was dissolved in 20 ml of n-butanol, and ammonium acetate (5.47 g, 71 mmol, 10 equiv.) was added. The mixture was reacted at 110°C under a nitrogen atmosphere for 24 h, then returned to room temperature. The solvent was evaporated, saturated brine was added, and the mixture was extracted twice with dichloromethane. The organic phase was dried over anhydrous sodium sulfate, concentrated and evaporated, and then directly proceeded to the next step. The obtained product was dissolved in 50 ml of anhydrous dichloromethane. N,N-diisopropylethylamine (2.75 g, 21.3 mmol, 3.0 equiv.) was added thereto at -20°C under a N2 atmosphere. After 10 minutes, boron trifluoride etherate (5.0 g, 35.5 mmol, 5.0 equiv.) was slowly added. The mixture was returned to room temperature and stirred for 12 hours. Saturated brine was then slowly added and extracted twice with dichloromethane. The organic phase was dried over anhydrous magnesium sulfate, filtered, concentrated, and spin-dried. Column chromatography was then performed using a mixed solution of dichloromethane and petroleum ether in a volume ratio of 1:1 as the eluent to obtain a brown solid product C5.

[0050] Synthesis of compound D5: Compound C5 (200 mg, 0.248 mmol, 1.0 equiv.) was added to a dry round-bottom flask, and 1,3-dimethylbarbituric acid (97 mg, 0.62 mmol, 2.5 equiv.) and tetrakistriphenylphosphine palladium (115 mg, 0.10 mmol, 0.4 equiv.) were added. Under a nitrogen atmosphere, anhydrous DMF (2 ml) was added as a solvent. After stirring at room temperature for 1-2 h, dichloromethane was added and the DMF was extracted multiple times with saturated brine to remove the DMF. The organic phase was dried over anhydrous sodium sulfate, spin-dried, and then subjected to column chromatography. The eluent for column chromatography was a mixed solution of DCM:CH3OH in a volume ratio of 95:5 to obtain a brown solid product D5. 2Cl OH–OBDP.

[0051] Example 1

[0052] A reactive oxygen species activated near-infrared photothermal reagent ROS-OBDP, whose structural formula is:

[0053]

[0054] The synthetic route of the ROS-OBDP is as follows:

[0055]

[0056] The preparation method of ROS-OBDP comprises the following steps:

[0057] Will 2Cl OH-OBDP (50 mg, 0.069 mmol, 1.0 equiv.), p-bromophenylboronic acid pinacol ester (59 mg, 0.207 mmol, 3.0 equiv.), and K2CO3 (29 mg, 0.207 mmol, 3.0 equiv.) were added to a 50-ml round-bottom flask. Under a nitrogen atmosphere, 5 mL of anhydrous acetonitrile was added, and the mixture was reacted at 60°C for 6 h. After filtration and extraction, column chromatography was performed to obtain 20 mg of a solid product with a yield of 25.1%. The eluent used for column chromatography was a mixed solvent of petroleum ether and dichloromethane in a 1:1 volume ratio.

[0058] That 1 H NMR (500MHz, CDCl3): δ8.13–7.94(m,8H),7.87(dd,J=7.9,3.2Hz,4H),7.58(d,J =7.7Hz,4H),7.05–6.88(m,6H),5.22–5.07(m,4H),3.90(s,6H),1.26(s,24H). Such as Figure 3 shown.

[0059] MALDI-TOF-MS(m / z):Calcd.for[M+Na] + ,1182.3324,found,1182.7412. Figure 4 shown.

[0060] Example 2

[0061] The preparation method of ROS-OBDP nanoparticles comprises the following steps:

[0062] 1 mg of ROS-OBDP was dissolved in 1 mL of dioxane and 2 mg of DSPE-PEG was added. 2k Dissolve in 10 mL of water and add the dioxane solution containing ROS-OBDP to the DSPE-PEG solution under high-speed stirring. 2k The sample was dialyzed for 24 h using a dialysis bag with a molecular weight cutoff of 3500 Da, and the water was changed every 4 h. The micellar nanoparticles were placed in a 4 ° C refrigerator for later use. Figure 5 shown.

[0063] Test Example 1

[0064] UV-Vis-NIR absorption spectra of ROS-OBDP nanoparticles in response to H2O2

[0065] ROS-OBDP micellar nanoparticles were dispersed in a PBS buffer solution at pH 7.4 to make the final concentration of the probe 20 μM. Different concentrations of H2O2 (0-10 mM) were added thereto. After incubation at 37 °C for 6 h, the UV-visible-near-infrared absorption spectrum was tested to obtain the detection limit of the probe, as shown in FIG. Figure 6 As shown in the figure, it can be seen that with the increase of H2O2 concentration, the absorption peak at 715nm gradually decreases, and the absorption peak at 775nm gradually increases. In the H2O2 concentration range of 0-0.8mM, the ratio of the absorption values at 775nm to 715nm shows a linear relationship with the concentration.

[0066] The ROS-OBDP micellar nanoparticles were dispersed in a PBS buffer solution at pH 7.4 to make the final concentration of the probe 20 μM, and then incubated with H2O2 at a final concentration of 5.0 mM at 37 °C. The UV-visible-near-infrared absorption spectra were tested at different time points of 0, 6, 12, 24, 30, and 48 h, respectively. Figure 7 As shown in Figure a, it can be seen from the figure that as the reaction proceeds, the absorption at 715nm gradually decreases and the absorption at 775nm gradually increases. After 30 hours of co-incubation, the absorption value basically no longer changes.

[0067] Meanwhile, ROS-OBDP micellar nanoparticles were dispersed in PBS buffer solution at pH 7.4 to make the final concentration of the probe 20 μM, and then incubated with H2O2 at final concentrations of 0.2, 0.5, 1.0, and 5.0 mM at 37 °C for 24 h, and the UV-visible-near-infrared absorption spectra were tested, as shown in Figure 5. Figure 7 As shown in Figure b, it can be seen from the figure that the ratio of the absorption peaks at 775nm and 715nm increases with the increase of H2O2 concentration. When the H2O2 concentration is 1.0mM and 5.0mM, after incubation for 30h, the ratio of the absorption peaks at 775nm and 715nm reaches equilibrium.

[0068] Test Example 2

[0069] Near-infrared fluorescence emission spectroscopy of ROS-OBDP nanoparticles in response to H2O2

[0070] ROS-OBDP micellar nanoparticles were dispersed in a PBS buffer solution at pH 7.4 to a final probe concentration of 20 μM. The probe was co-incubated with H2O2 at a final concentration of 10 mM at 37°C. The near-infrared fluorescence emission spectra were measured at different time points using a wavelength of 808 nm and a power of 1.5 W / cm 2 The laser is used for excitation and the wavelength is collected at 820-1200 nm. Figure 7 As shown in Figure c, it can be seen from the figure that after 12 hours of co-incubation, the emission at 912 nm increased by 21.3 times and tended to equilibrium.

[0071] At the same time, the PBS solution of ROS-OBDP nanoparticles with a final concentration of 10 μM was mixed with ClO - OH - 、 1 O2, NO, Cys, GSH, Hcy, NaSH, Na2SO4, Cu 2+ , Ca 2+ After incubation for 24 h, the fluorescence was measured to obtain the selectivity of the nanoprobe, such as Figure 7 As shown in Figure d, it can be seen from the figure that after ROS-OBDP nanoparticles are co-incubated with the above substances, the fluorescence hardly changes, which shows that the probe has good selectivity.

[0072] Test Example 3

[0073] In vitro photothermal experiments of ROS-OBDP micellar nanoparticles

[0074] ROS-OBDP micelle nanoparticles were dispersed in PBS buffer solution with a pH of 7.4 to a final probe concentration of 60 μM. After incubation with H2O2 at a final concentration of 5.0 mM at 37 °C for 24 h, the probe was detected using a wavelength of 808 nm and a power of 1.5 W / cm 2 The laser was used to illuminate the sample before and after the reaction with H2O2, and the temperature change with the illumination time was recorded. After 30 minutes of illumination, the light source was removed and the temperature change with time during the process of returning to room temperature was recorded. The photothermal efficiency before and after the reaction was calculated from this. At the same time, the concentration-dependent photothermal effect was also tested. Different concentrations of micelles that had completely reacted with H2O2 (concentrations were 10μM, 20μM, 40μM and 60μM, respectively) were illuminated at 808nm, 1.5W / cm 2 Under laser illumination, record the temperature changes over time, such as Figure 8 As shown, samples treated with H2O2 exhibited significantly superior photothermal effects compared to those not treated with H2O2, all other conditions remaining the same. Under 808nm laser irradiation, within 30 minutes, the temperature difference in the pure water group remained within 5°C, while that in the untreated group was 15°C. However, the temperature difference in the H2O2-treated group reached 35°C. The photothermal efficiency of the H2O2-treated samples reached 35.5%. The photothermal effect of the H2O2-treated samples showed significant concentration dependence. After 600 seconds of 808nm laser irradiation, the temperature differences in the pure water group were 13.3, 18.1, 24.5, and 27.8°C, respectively, at dye concentrations of 10, 20, 40, and 60 μM.

[0075] The calculation formula for photothermal efficiency is as follows:

[0076]

[0077] Where T max is 56.5℃, T surr is 21°C, A is the sample absorption value at 808nm, which is 0.761, and I is the laser power of 1.5W / cm 2 ,hA is calculated by the following formula,

[0078]

[0079] where m D The sample mass is 1.0 g, C D is the heat capacity (4.2 J / g), T s It can be calculated using the following formula:

[0080]

[0081] Where T RT is the temperature at each time point, T maxand T surr and room temperature respectively, so the calculated τ s The calculation results, combined with the above formula, finally calculated that the photothermal efficiency distribution before and after the reaction with H2O2 is 17.4% and 35.5%, as shown in Figure 9 shown.

[0082] The ROS-OBDP nanoparticles recovered to room temperature during the heating and cooling cycle after laser irradiation. Figure 8 As can be seen in Figure e, ROS-OBDP has good photostability. The highest temperature did not decrease significantly during several heating and cooling cycles. However, the photothermal effect of the commercial dye ICG (60 μM, pH 7.4) with the same concentration decreased significantly after several exposures. Figure 8 It can also be seen from Figure f in the figure that the absorption of ROS-OBDP did not change significantly after several temperature increases and decreases.

[0083] Application Example 1

[0084] Tumor Photothermal Imaging Using ROS-OBDP Nanoparticles

[0085] 4T1 cells were cultured at a rate of 1 × 10 7 The initial density of the vaccine was inoculated on the back of the tumor-bearing mice. Two weeks later, the tumor-bearing mice were divided into experimental and control groups, with 3 mice in each group. The tumor size of each group was about 100 mm. 3 Then, the experimental group of mice were injected with 200 μL of PBS solution with a concentration of 100 μg / mL ROS-OBDP nanoparticles through the tail vein. After 24 h, the nanoparticles were injected with a wavelength of 808 nm and a power of 1.5 W / cm 2 The laser was used to illuminate the tumor sites of the experimental and control mice, and then the changes of the biological characteristics of the tumor sites with the illumination time were recorded. Figure 10 As shown in the figure, it can be seen that after 10 minutes of illumination, the temperature of the experimental group injected with ROS-OBDP nanoparticles can rise to 60°C, while the temperature of the control group with simple illumination rises to 46°C, which also confirms that ROS-OBDP has a good photothermal effect at the in vivo level.

[0086] Application Example 2

[0087] Tumor photothermal therapy using ROS-OBDP nanoparticles

[0088] 4T1 cells were cultured at 1×10 7 The initial density of the vaccine was inoculated on the back of the tumor-bearing mice. Two weeks later, the tumor-bearing mice were divided into four groups, with 5 mice in each group. The tumor size was about 100mm. 3 , namely control group, light group, ROS-OBDP nanoparticle group, and ROS-OBDP nanoparticle plus light group.

[0089] The ROS-OBDP nanoparticles group and the ROS-OBDP nanoparticles plus light irradiation group were injected with 200 μL of PBS solution of ROS-OBDP nanoparticles with a concentration of 100 μg / mL. The light irradiation group and the ROS-OBDP nanoparticles plus light irradiation group were irradiated with a wavelength of 808 nm and a power of 1.5 W / cm 2 The laser was irradiated for 10 minutes. The tumor volume and weight of the mice in each group were measured every 3 days. After 21 days of treatment, the tumor tissue was removed and macroscopic photos of the tumor were taken. The average tumor weight of each group after the treatment was calculated. Figure 11 As shown in the figure, it can be seen that in the experimental group with only light and nanoparticles, the tumor volume almost did not change or even disappeared, while the tumor volumes of the other three groups gradually increased. Figure 10 Figure a in . Figure 11 Figure b shows a macroscopic photo of the mouse tumor after the experiment. It can be seen that the experimental group treated with only nanoparticles and light can significantly inhibit tumor growth. Figure 11 Figure c in the figure is the final average value of tumor mass in each group. Figure 11 Figure d shows the weight changes of mice during the entire treatment process.

[0090] The above-mentioned detailed description of an active oxygen-activated near-infrared photothermal reagent, its preparation method, and application with reference to the embodiments is illustrative rather than restrictive. Several embodiments can be listed according to the limited scope. Therefore, changes and modifications without departing from the overall concept of the present invention should fall within the scope of protection of the present invention.

Claims

1. A near-infrared photothermal reagent activated by active oxygen, characterized in that: The structural formula of the active oxygen activated near-infrared photothermal reagent is:

2. The method for preparing the active oxygen activated near-infrared photothermal reagent according to claim 1, wherein: The preparation method comprises the following steps: 2Cl OH-OBDP is mixed with 4-bromomethylphenylboronic acid pinacol ester and an inorganic base, and an organic solvent is added under an inert atmosphere. The mixture is reacted at 55-65°C for 6-12 hours, and then post-treated to obtain an active oxygen-activated near-infrared photothermal reagent. described 2Cl The structural formula of OH-OBDP is:

3. The preparation method according to claim 2, characterized in that 2Cl The molar ratio of OH-OBDP, 4-bromomethylphenylboronic acid pinacol ester and inorganic base is 1:2-3:2-3.

4. The preparation method according to claim 2, characterized in that The inorganic base is one of potassium carbonate and sodium carbonate.

5. The preparation method according to claim 2, characterized in that The inert gas is nitrogen.

6. The preparation method according to claim 2, characterized in that The organic solvent is anhydrous acetonitrile.

7. A reactive oxygen species activated near-infrared photothermal agent nanoparticle, characterized in that: The preparation method is as follows: the active oxygen activated near-infrared photothermal agent according to claim 1 is dissolved in an organic solvent miscible with water, and then added into water containing a surfactant under high-speed stirring.

8. The active oxygen activated near-infrared region photothermal agent nanoparticles according to claim 7, characterized in that: The water-miscible organic solvent is any one or more of dioxane, dimethyl sulfoxide, and N,N-dimethylformamide.

9. The active oxygen activated near-infrared photothermal reagent according to claim 1, characterized in that The surfactant is DSPE-PEG 2000 , Tween 80, or F127.

10. Use of the reactive oxygen species activated near-infrared region photothermal agent nanoparticles according to claim 7 in preparing a tumor photothermal imaging agent or a tumor photothermal therapy agent.

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