Near-infrared two-region light diagnosis and treatment functional molecule based on sulfur-sulfur space interaction, nano probe and application of near-infrared two-region light diagnosis and treatment functional molecule and nano probe

Abstract

The invention relates to the technical field of biomedical materials and cancer treatment, in particular to a near-infrared two-region optical diagnosis and treatment functional molecule based on sulfur-sulfur space interaction, a nano probe and application of the near-infrared two-region optical diagnosis and treatment functional molecule and the nano probe. According to the invention, the sulfur-sulfur space interaction is utilized for the first time to construct the NIR-II light diagnosis and treatment functional molecule, through cross-space conjugate extension and conformation locking, the limitation of energy gap law is broken through, long-wavelength emission and high fluorescence quantum yield are realized, and the method has important significance for promoting the development of a precise cancer diagnosis and treatment technology.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials and cancer treatment technology, specifically to a near-infrared II phototherapy functional molecule, nanoprobe, and its application based on sulfur-sulfur spatial interactions. Background Technology

[0002] Cancer, as a major disease threatening human health, faces numerous limitations with traditional treatment methods (surgical resection, radiotherapy, and chemotherapy), including systemic toxicity, drug resistance, and the separation of diagnosis and treatment. Near-infrared II (NIR-II, 700-1700 nm) phototherapy, with its advantages of deep tissue penetration, high signal-to-noise ratio imaging, and precise photothermal therapy, has become a research hotspot in integrated cancer diagnosis and treatment. However, constrained by the "bandgap law," traditional NIR-II organic photothermal reagents experience a significant reduction in fluorescence quantum yield when achieving long-wavelength emission, making it difficult to simultaneously meet the demands of high-sensitivity imaging and efficient photothermal therapy.

[0003] Current probes used for NIR-II imaging and photothermal therapy (such as small molecule dyes, quantum dots, nanoparticles, etc.) have key performance contradictions and defects, mainly including: 1) Difficulty in achieving both fluorescence and photothermal performance: According to the "energy gap law", if traditional probes pursue long emission wavelengths (to match the NIR-II window), it is often accompanied by a decrease in quantum yield (QY), and there is a trade-off between photothermal conversion efficiency and fluorescence efficiency, which cannot simultaneously meet the requirements of high-definition imaging and efficient treatment; 2) Molecular design limitations: Most probes rely on the extension of intramolecular conjugated structures to achieve long-wavelength emission, but excessive conjugation can easily lead to molecular aggregation and decreased stability, and lacks precise control over intermolecular interactions; Currently, "through-space interaction" has received widespread attention in molecular design. It is mainly achieved by regulating molecular conformation (such as dihedral angles) and intermolecular non-covalent interactions (such as SS interactions, van der Waals forces, and hydrogen bonds) to enhance electron delocalization and increase molecular rigidity, thereby simultaneously optimizing emission wavelength, quantum yield, and photothermal properties. However, existing research lacks a sufficient understanding of the mechanisms of this type of interaction, systematic theoretical calculations and experimental verification, and a mature "interaction regulation - performance optimization - biological application" technical system has not yet been formed. Therefore, developing more high-performance NIR-II phototherapy nanoprobes is of great significance for promoting the development of precision cancer diagnosis and treatment technologies. Summary of the Invention

[0004] The purpose of this invention is to provide a NIR-II phototherapy functional molecule and nanoprobe based on sulfur-sulfur spatial interaction, which solves the problem that traditional NIR-II probes cannot simultaneously achieve long-wavelength emission and high fluorescence efficiency, and realizes precise imaging-guided photothermal therapy for tumors.

[0005] On the one hand, the present invention protects a near-infrared II phototherapy functional molecule based on sulfur-sulfur spatial interaction, which is a compound as shown in formula (I), or a stereoisomer, geometric isomer or pharmaceutically acceptable salt of the compound shown in formula (I). (I); in: X and Y are independently O, S, or Se, respectively; R1, R2, R3, and R4 are each independently C 6-12 Straight-chain alkyl; R5, R6, R7, R8, R9, R 10 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 Halogenated alkoxy groups.

[0006] In some implementation schemes, both X and Y are S.

[0007] In some embodiments, R1, R2, R3, and R4 are independently C6 straight-chain alkyl, C7 straight-chain alkyl, C8 straight-chain alkyl, C9 straight-chain alkyl, and C6 straight-chain alkyl, respectively. 10 straight-chain alkyl, C 11 straight-chain alkyl, C 12 Straight-chain alkyl groups.

[0008] In some implementations, R1 and R3 are both straight-chain C8H 17 R2 and R4 are both straight-chain C 10 H 21。

[0009] In some implementation schemes, R5, R6, R7, R8, R9, R 10Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -CH2CF2CHF2, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, -OCHF2, -OCF3, -OCHFCH2F, -OCF2CHF2, -OCH2CF3, or -OCH2CF2CHF2.

[0010] In some embodiments, it is a compound having one of the following structures or a stereoisomer, geometric isomer, or pharmaceutically acceptable salt of a compound having one of the following structures: , , , .

[0011] On the other hand, the present invention also protects a phototherapy nanoprobe comprising the aforementioned near-infrared II phototherapy functional molecules, and a matrix for encapsulating the aforementioned functional molecules.

[0012] In some embodiments, the matrix is ​​Pluronic F127 or DSPE-PEG2000.

[0013] In some implementations, the preparation method of the nanoprobe includes the following steps: (1) Dissolve Pluronic F-127 in deionized water to prepare an aqueous solution with a mass concentration of 1-5 mg / mL as the aqueous phase; (2) Dissolve the functional molecules of Quanguang diagnosis and treatment in tetrahydrofuran to prepare an organic phase with a concentration of 0.1-1 mg / mL; (3) Under ultrasonic conditions, add the organic phase dropwise to the aqueous phase, with a volume ratio of organic phase to aqueous phase of 1:5-1:20, and continue ultrasonication for 10-30 minutes. (4) Tetrahydrofuran in the system was removed by rotary evaporation and filtered through a 0.22 μm filter membrane to obtain an aqueous solution of nanoprobe.

[0014] On the other hand, the present invention also protects the application of the above-mentioned near-infrared II phototherapy functional molecules and phototherapy nanoprobes in the preparation of NIR-II fluorescence imaging reagents, tumor photothermal therapy reagents or integrated tumor phototherapy reagents.

[0015] In some implementations, the nanoprobe can be used for in vivo tumor imaging and vascular imaging, with imaging performed using an 808 nm laser for excitation and fluorescence signals acquired through a 1300 nm long-pass filter.

[0016] In some embodiments, the nanoprobe can generate a highly efficient photothermal effect under 808 nm laser irradiation, for the precise photothermal treatment of tumor cells in vitro and tumor tissue in vivo, with a laser power density of 0.4-0.8 W / cm².

[0017] In some implementations, the nanoprobe can simultaneously achieve NIR-II fluorescence imaging guidance and photothermal therapy for cancer diagnosis, treatment, and efficacy monitoring.

[0018] In some implementations, the tumor includes solid tumors such as breast cancer, lung cancer, liver cancer, and colon cancer, preferably 4T1 breast cancer.

[0019] The present invention has achieved the following beneficial effects: (1) This invention is the first to utilize sulfur-sulfur spatial interaction to construct NIR-II phototherapy functional molecules. Through cross-spatial conjugation extension and conformation locking, it breaks through the "bandgap law" limitation and achieves synergistic optimization of long wavelength (>1100 nm) emission and high fluorescence quantum yield (0.3%). Compared with molecules without sulfur-sulfur spatial interaction, the performance is significantly improved. (2) The nanoprobe prepared by the present invention has strong light absorption ability at 808 nm (molar absorptivity 40000 cm⁻¹M⁻¹), and photothermal conversion efficiency of more than 24%. It can achieve efficient tumor ablation under low power laser irradiation, reducing damage to normal tissues. (3) The nanoprobe prepared by the present invention has excellent NIR-II fluorescence imaging performance, high signal-to-background ratio, and can clearly display the tumor vascular network and tumor boundary, providing precise guidance for photothermal therapy; (4) The nanoprobe prepared by the present invention has good water solubility and high biosafety. No obvious toxic side effects were observed in in vivo experiments, and it has good clinical translation potential.

[0020] Unless otherwise stated, the following definitions will apply in this invention. For the purposes of this invention, chemical elements are defined according to the periodic table, CAS version, and the Chemical Handbook, 75th Ed, 1994. Furthermore, general principles of organic chemistry are found in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007; therefore, all content incorporates these references.

[0021] The term "alkyl" as used in this invention includes a monovalent hydrocarbon group with 1-20 carbon atoms, or 1-10 carbon atoms, or 1-6 carbon atoms, or 1-4 carbon atoms, or 1-3 carbon atoms, or 1-2 carbon atoms, consisting of a saturated straight-chain or branched chain, wherein the alkyl group may be independently and optionally substituted by one or more substituents described in this invention. Further examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), isobutyl (i-Bu, -CH2CH(CH3)2), sec-butyl (s-Bu, -CH(CH3)CH2CH3), tert-butyl (t... -Bu, -C(CH3)3), n-pentyl (-CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl (-CH2CH2CH(CH3)2), 2-methyl -1-Butyl (-CH2CH(CH3)CH2CH3), n-Hexyl (-CH2CH2CH2CH2CH2CH3), 2-Hexyl (-CH(CH3)CH2CH2CH2CH3), 3-Hexyl (-CH(CH2CH3)(CH2CH2CH3)), 2-Methyl-2-pentyl (-C(CH3)2CH2CH2CH3), 3-Methyl-2-pentyl (-CH(CH3)CH(CH3)CH2C) H3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3), n-heptyl, and n-octyl, etc. The term "alkyl" and its prefix "alkane" are used here, both encompassing straight-chain and branched saturated carbon chains.

[0022] The term "alkoxy" or "alkyloxy" as used in this invention refers to an alkyl group, as defined herein, that is attached to other parts of a compound molecule via an oxygen atom. In some embodiments, the alkoxy group is C10. 1-4 Alkoxy groups; examples of which include, but are not limited to, methoxy, ethoxy, propoxy, and butoxy groups. Furthermore, the alkoxy group may be independently unsubstituted or substituted by one or more substituents described in this invention.

[0023] A ring system formed by a substituent connected to a ring by a bond means that the substituent can be substituted at any substituted position on the ring. For example, formula (a) means that the substituent R can be monosubstituted or polysubstituted at any possible substituted position on the pyridine ring.

[0024] Unless otherwise explicitly stated, the descriptive phrases “each and each is independently”, “each and each is independently”, and “each and each is independently” used throughout this document are interchangeable and should be interpreted broadly. They can mean either that the specific options expressed by the same symbols in different groups do not affect each other, or that the specific options expressed by the same symbols in the same group do not affect each other.

[0025] Unless otherwise indicated, the structural formulas described in this invention include all isomers (e.g., enantiomers, diastereomers, geometric isomers, or conformational isomers): for example, R and S configurations containing an asymmetric center, (Z) and (E) isomers of double bonds, and (Z) and (E) conformational isomers. Therefore, any single stereochemical isomer of the compounds of this invention, or a mixture of its enantiomers, diastereomers, geometric isomers, or conformational isomers, is within the scope of this invention.

[0026] The term "pharmaceutically acceptable salt" as used in this invention refers to the organic and inorganic salts of the compounds of this invention. Pharmaceutically acceptable salts are well-known in the field, as described in the literature: SMBerge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 66:1-19, 1977. Salts formed from pharmaceutically acceptable non-toxic acids include, but are not limited to: inorganic acid salts formed by reaction with amino groups, such as hydrochlorides, hydrobromic acids, phosphates, sulfates, and perchlorates; organic acid salts, such as acetates, oxalates, maleates, tartrates, citrates, succinates, and malonates; or salts obtained by other methods described in the literature, such as ion exchange. Other pharmaceutically acceptable salts include adipate, malate, 2-hydroxypropionate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, cyclopentylpropionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, transbutenedioic acid, gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, palmitate, pyrate, pectinate, persulfate, 3-phenylpropionate, picrate, pentanoate, propionate, stearate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0027] Unless otherwise stated herein or the context clearly indicates otherwise, the terms “an,” “a,” “the,” and similar terms used herein, as well as in the context of the invention (especially in the context of the claims), may be interpreted as including both the singular and the plural. Attached Figure Description

[0028] Figure 1 The image shows a comparison of the photophysical properties of compounds NTPD and NPTD. (1a) shows the absorption spectrum in THF solution. Inset: Photographs of molecular solutions of compounds NTPD and NPTD. (1b) shows the fluorescence emission spectrum in THF solution (concentration of 10 μM). (1c) shows the fluorescence emission spectrum in deuterated THF solution. (1d) shows the emission spectrum in the PMMA (0.1%) doping state. (1e) shows the maximum emission wavelength under different conditions. (1f) shows the fluorescence quantum yield.

[0029] Figure 2The images show in vivo imaging of NTPD NPs. (2a) Near-infrared II (NIR-II) fluorescence images of NTPD nanoparticles (top row) and indocyanine green (bottom row) at different concentrations (0.06, 0.13, 0.25, 0.5, 1.0 mg / mL) in deionized water, using an 808 nm laser as the excitation source. (2b) Fluorescence intensity was quantified using Image J (n=3, mean ± standard deviation). (2c) Fluorescence images of mouse blood vessels. (2d) Quantitative analysis of vascular fluorescence. (2e, 2f) Near-infrared II fluorescence images of 4T1 tumor-bearing mice taken at different monitoring time points after intravenous injection of NTPD nanoparticles. (2g, 2h) Ex vivo fluorescence images and average fluorescence signal intensity of tumors and major organs dissected from mice 24 hours after injection.

[0030] Figure 3 The in vivo photothermal therapy-related atlases of NTPD NPs are shown below; (3a) is a schematic diagram of the treatment plan; (3b) is a photothermal image of the tumor site; (3c) is a curve showing the change in tumor temperature; (3d) is a curve showing the growth of tumor volume; (3e) is a curve showing the change in mouse body weight; (3f) is a photograph of the tumor after treatment; and (3g) is an H&E staining image of the major organs. Detailed Implementation

[0031] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] The endpoints and any values ​​of the ranges described in this invention are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein. The raw materials and reagents used in the following examples are commercially available.

[0033] Preparation Example 1: Preparation of Compound NTPD

[0034] Step 1: Preparation of compound NDI-T1 NDI-2Br (0.1 mmol), 2-(tributyltinyl)thiophene (0.2 mmol), and tetrakis(triphenylphosphine)palladium (0.033 mmol) were dissolved in anhydrous toluene (10 mL), and the mixture was refluxed at 110 °C overnight under nitrogen protection. After the reaction was completed, the mixture was cooled to room temperature, extracted with n-hexane, washed with water and brine, and the organic phase was concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (eluent: n-hexane / dichloromethane = 1 / 2) to give compound NDI-T1 in 81.2% yield.

[0035] Step 2: Preparation of compound NDI-T2 Compound NDI-T1 (0.01 mmol) and THF (10 mL) were added to a round-bottom flask equipped with a magnetic stirrer, followed by the slow addition of N-bromosuccinimide (0.02 mmol). The mixture was stirred overnight at room temperature. After the reaction was complete, the mixture was extracted with dichloromethane and concentrated under reduced pressure. The crude product was purified by column chromatography to give compound NDI-T2 in 90.3% yield.

[0036] Under nitrogen atmosphere, compound NDI-T2 (0.1 mmol), (4-(diphenylamino)phenyl)boronic acid (0.24 mmol), and potassium carbonate (0.033 mmol) were dissolved in tetrahydrofuran (10 mL) and water (4 mL), followed by the addition of tetra(triphenylphosphine)palladium (0.033 mmol). The mixture was heated to 100 °C and refluxed for 12 h. After the reaction was complete, the mixture was cooled to room temperature, extracted with dichloromethane, washed three times with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (eluent: petroleum ether / dichloromethane = 3 / 1) to give compound NTPD in 70% yield.

[0037] MS (ESI) m / z calcd. for C 104 H 114 N6O4S6H + : 1703.7259, Found: 1704.7340.

[0038]

[0039] NDI-P-1 (0.1 mmol), N,N-diphenyl-5-(tributyltinyl)-2-thiopheneamine (0.2 mmol), and tetrakis(triphenylphosphine)palladium (0.033 mmol) were dissolved in anhydrous toluene (10 mL), and the mixture was refluxed at 110 °C overnight under nitrogen protection. After the reaction was completed, the mixture was cooled to room temperature, extracted with n-hexane, washed with water and brine, and the organic phase was concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography (eluent: n-hexane / dichloromethane = 1 / 2) to give compound NPTD in 60.5% yield.

[0040] MS (ESI) m / z calcd. for C 104 H 114 N6O4S6 Na + : 1726.7259, Found: 1726.7097. Preparation Example 3: Preparation of NTPD Nanoprobes (NTPD NPs) (1) Add Pluronic F-127 (100 mg) to 20 mL of deionized water and stir magnetically until completely dissolved to obtain an aqueous solution of 5 mg / mL, which is used as the aqueous phase; (2) Weigh NTPD (2 mg) and dissolve it in 2 mL of tetrahydrofuran. Dissolve by sonication to obtain an organic phase of 1 mg / mL. (3) Under ultrasonic conditions (power 100 W), the organic phase is added dropwise to the aqueous phase and ultrasonication is continued for 20 minutes to form a uniform suspension; (4) Place the suspension in a rotary evaporator and distill under reduced pressure at 35°C for 30 minutes to remove tetrahydrofuran; (5) The obtained solution was filtered through a 0.22 μm filter membrane to obtain an aqueous solution of NTPD NPs with a concentration of 0.1 mg / mL, which was stored at 4℃ protected from light.

[0041] Preparation Example 4: Preparation of NPTD Nanoprobes (NPTD NPs) (1) Add Pluronic F-127 (100 mg) to 20 mL of deionized water and stir magnetically until completely dissolved to obtain an aqueous solution of 5 mg / mL, which is used as the aqueous phase; (2) Weigh NPTD (2 mg) and dissolve it in 2 mL of tetrahydrofuran. Dissolve by sonication to obtain an organic phase of 1 mg / mL. (3) Under ultrasonic conditions (power 100 W), the organic phase is added dropwise to the aqueous phase and ultrasonication is continued for 20 minutes to form a uniform suspension; (4) Place the suspension in a rotary evaporator and distill under reduced pressure at 35°C for 30 minutes to remove tetrahydrofuran; (5) The obtained solution was filtered through a 0.22 μm filter membrane to obtain an aqueous solution of NPTD NPs with a concentration of 0.1 mg / mL, which was stored at 4℃ protected from light.

[0042] The absorption and fluorescence emission spectra of compounds NTPD and NPTD in THF solution, deuterated THF solution, and PMMA-doped system (intramolecularly restricted RIM state) were measured. The results are shown below. Figure 1 a-1f.

[0043] Depend on Figure 1 As can be seen from a, 1b, and 1e, both compounds NTPD and NPTD exhibit near-infrared absorption and emission characteristics. The maximum absorption peak of compound NTPD in THF is located at 755 nm, and the maximum emission peak is located at 1110 nm, which is about 100 nm redshifted from the wavelength of compound NPTD. Figure 1 c represents the fluorescence emission spectrum in deuterated THF solvent, which corrects for peak distortion caused by the solvent CH vibration peak. Figure 1 As can be seen from d, the compound NTPD retains a long emission wavelength and strong fluorescence intensity even after being doped into a thin film. From Figure 1 As shown in f, the fluorescence quantum yield of compound NTPD is ten times that of compound NPTD. These results indicate that the photophysical properties of the isomers differ significantly, and that compound NTPD can overcome the bandgap law to achieve longer wavelength emission and higher quantum efficiency.

[0044] The in vivo imaging performance of NTPD nanoparticles was evaluated. The testing method is as follows: Whole-body vascular imaging in mice: Healthy mice were injected with 200 μL of NTPD nanoparticle aqueous dispersion (concentration 1 mg / mL) via the tail vein. Following injection, whole-body fluorescence scanning was performed using a near-infrared II (NIR-II) imaging system. Fluorescence signals were collected using long-pass filters (LP) at 900 nm, 1100 nm, and 1300 nm. The signal-to-background ratio (SBR) under different filters was analyzed using software, and the spatial frequency distribution of the images was analyzed using Fast Fourier Transform (FFT) to evaluate the imaging sharpness at different wavelengths. 2. Tumor accumulation and in vivo fluorescence imaging: A 4T1 tumor-bearing mouse model was constructed. Once the tumor volume reached a preset size, the aforementioned NTPD nanoparticles were injected via the tail vein. Fluorescence distribution within the mice was recorded at different time intervals after injection (e.g., 0, 2, 4, 8, 12, 24 h). The metabolic kinetics of the nanoparticles were evaluated by quantitatively analyzing the changes in fluorescence intensity over time at the tumor site and other organs. 3. Biodistribution assay: Mice were euthanized 24 hours after nanoparticle injection, and heart, liver, spleen, lung, kidney, and tumor tissues were collected in vitro. The fluorescence intensity of each isolated organ was measured to evaluate the biodistribution characteristics of the nanoparticles in vivo. Results are shown below. Figure 2 a-2h.

[0045] Depend on Figure 2 As shown in a-2b, NTPD NPs have significantly better imaging performance than commercially available fluorescent dye indocyanine green (ICG) in near-infrared II (NIR-II) imaging systems.

[0046] Depend on Figure 2 As shown in c-2h, NTPD NPs have excellent NIR-II fluorescence imaging performance, with a high signal-to-background ratio, which can clearly display the tumor vascular network and tumor boundary, providing precise guidance for photothermal therapy.

[0047] The in vivo photothermal therapy efficacy of NTPD nanoparticles was evaluated. The test methods are as follows: 1) A 4T1 tumor-bearing mouse model was constructed, and experiments were conducted 7 days after tumor growth. Mice in the experimental group were injected with NTPD nanoparticles (1 mg / mL, 200 μL) via the tail vein, while the control group was injected with an equal volume of PBS buffer. An 808 nm laser (power density 0.6 W cm⁻¹) was used. -2 The tumor site was irradiated, and the temperature change of the tumor area was recorded within 10 minutes using an infrared thermal imager.

[0048] 2) After treatment, the mice were euthanized, and the main organs such as heart, liver, spleen, lungs and kidneys were collected for H&E staining. Pathological examination of the sections showed no obvious tissue damage.

[0049] As shown in Figures 3b-3c, at low power density (0.6 W / cm²), -2 Under laser irradiation, the temperature of the tumor region injected with NTPD nanoparticles rapidly rose to above 50 °C within 2 minutes and reached approximately 55 °C after 10 minutes; while the PBS control group showed no significant temperature change under the same conditions. These results demonstrate that the NTPD nanoparticles described in this invention possess extremely high photothermal conversion capabilities, efficiently converting near-infrared light into heat energy to kill tumor cells.

[0050] Depend on Figure 3 As shown in d and 3f, the tumors in the "NTPD NPs+NIR" treatment group completely regressed within 2-4 days, and no recurrence occurred during the subsequent 14-day observation period, indicating that NTPD nanoparticles have excellent PTT therapeutic performance. In contrast, the tumor growth rate in the control group, which only received nanoparticle injections or only underwent laser irradiation, was no different from that in the PBS group, indicating that laser or material alone had no therapeutic effect.

[0051] Depend on Figure 3 As shown in the figure, the weight of mice in each group did not decrease significantly during the treatment period, proving that the treatment regimen is safe for individual mice while effectively eliminating tumors.

[0052] Depend on Figure 3 As can be seen from g, no morphological abnormalities or tissue damage were found in the H&E stained sections of the major organs. Therefore, the NTPD nanoparticles described in this invention have good biocompatibility and can be used as a nanoaggregate integrating fluorescence imaging guidance and photothermal therapy for optical diagnosis and treatment of cancer.

[0053] The above embodiments are merely illustrative examples and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A near-infrared II phototherapy functional molecule based on sulfur-sulfur spatial interaction, which is a compound as shown in formula (I), or a stereoisomer, geometric isomer or pharmaceutically acceptable salt of the compound shown in formula (I). （I）； in: X and Y are independently O, S, or Se, respectively; R1, R2, R3, and R4 are each independently C 6-12 Straight-chain alkyl; R5, R6, R7, R8, R9, R 10 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, and C. 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl groups and C 1-6 Halogenated alkoxy groups.

2. The near-infrared II phototherapy functional molecule according to claim 1, characterized in that, Both X and Y are S.

3. The near-infrared II phototherapy functional molecule according to claim 1, characterized in that, R1, R2, R3, and R4 are independently C6 straight-chain alkyl, C7 straight-chain alkyl, C8 straight-chain alkyl, C9 straight-chain alkyl, and C4 straight-chain alkyl, respectively. 10 straight-chain alkyl, C 11 straight-chain alkyl, C 12 Straight-chain alkyl groups.

4. The near-infrared II phototherapy functional molecule according to claim 1, characterized in that, R1 and R3 are both straight-chain C8H 17 R2 and R4 are both straight-chain C 10 H 21 .

5. The near-infrared II phototherapy functional molecule according to claim 1, characterized in that, R5, R6, R7, R8, R9, R 10 Each of the following is independently selected from H, D, F, Cl, Br, I, OH, NH2, CN, NO2, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, -CHF2, -CF3, -CHFCH2F, -CF2CHF2, -CH2CF3, -CH2CF2CHF2, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, -OCHF2, -OCF3, -OCHFCH2F, -OCF2CHF2, -OCH2CF3, or -OCH2CF2CHF2.

6. The near-infrared II phototherapy functional molecule according to claim 1, wherein it is a compound having one of the following structures or a stereoisomer, geometric isomer, or pharmaceutically acceptable salt of a compound having one of the following structures: 、 、 、 。 7. A phototherapy nanoprobe, comprising the near-infrared II phototherapy functional molecule as described in any one of claims 1-6, and a matrix for encapsulating the aforementioned functional molecule.

8. The phototherapy nanoprobe according to claim 7, characterized in that the matrix is ​​Pluronic F127 or DSPE-PEG2000.

9. The use of the near-infrared II phototherapy functional molecule according to any one of claims 1-6 and the phototherapy nanoprobe according to claim 7 in the preparation of NIR-II fluorescence imaging reagents, tumor photothermal therapy reagents or integrated tumor phototherapy reagents.

10. The application according to claim 9, characterized in that, The tumors were selected from breast cancer, lung cancer, liver cancer, and colon cancer.

Images