A TPP-modified PAMAM-loaded Cyl mitochondrial-targeted nanophotosensitive system, its preparation method and application

Abstract

This invention belongs to the field of photosensitizer delivery and photodynamic therapy technology, and discloses a TPP-modified PAMAM-loaded CyI mitochondrial-targeting nanophotosensitive system, its preparation method, and its applications. This invention aims to solve the problems of poor water dispersibility, insufficient in vivo stability, low delivery efficiency, and lack of mitochondrial targeting ability of CyI during application. The nanophotosensitive system consists of G5 generation PAMAM dendritic macromolecules, triphenylphosphine-based mitochondrial-targeting groups (TPP), and the near-infrared photosensitizer CyI. The preparation method involves first coupling TPP with G5 generation PAMAM to obtain a modified carrier, then mixing and purifying it with CyI to obtain the target nanophotosensitive system. This system is beneficial for improving the stability and delivery efficiency of CyI and enhancing its enrichment ability in tumor mitochondria, showing promising application prospects in tumor near-infrared fluorescence imaging and photodynamic therapy.

Description

Technical Field

[0001] This invention belongs to the field of photosensitizer delivery and photodynamic therapy technology, and particularly relates to a mitochondrial-targeted nanophotosensitive system modified with TPP (triphenylphosphine bromide) and loaded with Cyl (iodinated anthocyanin dye), its preparation method and application. Background Technology

[0002] Photodynamic therapy (PDT), as an emerging tumor treatment method, has attracted widespread attention in the field of tumor treatment due to its advantages such as non-invasiveness, strong spatiotemporal controllability, and low systemic toxicity. Among them, iodinated cyanine dyes (CyI), as photosensitizers, possess near-infrared fluorescence imaging capabilities, singlet oxygen generation capabilities, and photothermal conversion properties, and have good application potential in the field of tumor phototherapy.

[0003] However, CyI still faces significant limitations in practical applications. On one hand, CyI is a hydrophobic molecule, exhibiting poor dispersibility in biological systems and a tendency to aggregate, affecting its stability and bioavailability. On the other hand, free CyI lacks effective carrier protection during in vivo delivery, resulting in limited stability and difficulty in achieving efficient accumulation at tumor sites. Furthermore, CyI lacks effective subcellular localization capabilities after entering cells, making it difficult to accumulate sufficiently at specific sites of action, thus limiting its further potential in imaging and phototherapy.

[0004] Mitochondria, as important energy metabolism centers and the core of programmed cell death regulation within cells, play a crucial role in cellular oxidative stress and signal transduction. Because mitochondria are highly sensitive to reactive oxygen species, if photosensitizers can target and accumulate in mitochondria within cells, the cell damage effect induced by photodynamic therapy can be significantly amplified, enhancing the killing ability against tumor cells.

[0005] However, current technologies lack a delivery system that can simultaneously achieve stable CyI loading, efficient delivery, and mitochondrial-targeted enrichment capabilities, hindering CyI from realizing its maximum therapeutic potential in vivo. Therefore, developing a novel drug delivery system that combines stable CyI delivery and mitochondrial-targeted enrichment capabilities is of great significance for improving CyI utilization efficiency and enhancing the efficacy of photodynamic therapy for tumors.

[0006] Based on the above analysis, the problems and shortcomings of the existing technology are as follows: There is currently a lack of a delivery system that can balance stable CyI loading, effective delivery, and mitochondrial targeting enrichment capabilities, which makes it difficult for CyI to realize its maximum therapeutic potential in vivo. Summary of the Invention

[0007] To address the problems existing in the prior art, this invention provides a mitochondrial-targeted nanophotosensitive system with TPP-modified PAMAM and Cyl loading, its preparation method, and its application.

[0008] This invention is achieved as follows: a mitochondrial-targeted nanophotosensitive system with TPP-modified PAMAM loaded with CyI is a composite system formed by TPP-modified PAMAM loaded with CyI.

[0009] Furthermore, the PAMAM is a polyamide-amine dendritic macromolecule, more preferably a fifth-generation polyamide-amine dendritic macromolecule. Its surface contains abundant amino structures.

[0010] Furthermore, the TPP is covalently coupled to the amino groups on the surface of PAMAM, thereby endowing the nanosystem with mitochondrial targeting capability.

[0011] Furthermore, the CyI is loaded into the internal cavity and molecular structure of the TPP-modified PAMAM through hydrophobic and electrostatic interactions, thereby forming a stable nanocomposite system.

[0012] Another object of the present invention is to provide a method for preparing the above-mentioned mitochondrial-targeted nanophotosensitive system, comprising the following steps: (1) React TPP with PAMAM to covalently link TPP to the surface of PAMAM to obtain a TPP-modified PAMAM carrier. (2) CyI is mixed and incubated with the TPP-modified PAMAM vector to load CyI into the vector; (3) The obtained system was purified to obtain the mitochondrial-targeted nanophotosensitive system.

[0013] Furthermore, the coupling reaction described in step (1) is an amidation reaction based on amino groups on the PAMAM surface.

[0014] Furthermore, in step (2), stirring or ultrasonic assistance is used to promote the loading of CyI.

[0015] Another objective of this invention is to provide the application of the above-mentioned mitochondrial-targeted nanophotosensitive system in the preparation of antitumor drugs.

[0016] Based on the above technical solutions and the technical problems solved, please analyze the advantages and positive effects of the technical solution to be protected by this invention from the following aspects: This invention improves the water dispersibility and in vivo stability of CyI by using PAMAM carrier, and reduces its aggregation.

[0017] CyI is a hydrophobic iodinated anthocyanin near-infrared photosensitizer that readily forms H-aggregates in aqueous solutions, exhibiting insufficient dispersibility and a risk of aggregation. This invention encapsulates CyI with PAMAM dendritic macromolecules, transforming it from a free hydrophobic small molecule into a nanocomposite system. Results show that the resulting system consists of uniformly dispersed spherical nanoparticles with a hydrated particle size of 92.93±2.59 nm, a PDI of 0.27±0.06, and a zeta potential of +19.7 mV; the CyI encapsulation efficiency reaches 89.52%, and the drug loading rate is 8.08%. These results demonstrate that PAMAM can effectively accommodate CyI and form a well-defined, relatively uniformly dispersed nanostructure, thereby reducing the risk of direct aggregation of CyI in an aqueous environment.

[0018] This invention improves the in vivo delivery efficiency and tumor site enrichment capacity of CyI through a nanodelivery system.

[0019] Free CyI was virtually undetectable in plasma 4 hours after intravenous administration, mainly distributed in metabolic or excretion-related tissues such as the liver, kidneys, and intestines, and was largely cleared from the body after 24 hours. This suggests that free CyI has a limited retention time in vivo. This invention loads CyI onto a TPP-PAMAM nanocarrier to form a nanodelivery system. The hydrated particle size of this system is 92.93±2.59 nm, greater than the rapid renal clearance threshold but less than 200 nm, providing a structural basis for tumor tissue penetration and retention through the EPR effect caused by increased vascular permeability and insufficient lymphatic drainage in tumor tissue. In vivo near-infrared fluorescence imaging results showed that the fluorescence signal at the tumor site gradually increased within 10 hours after intravenous injection of the nanosystem and could be retained up to 24 hours; ex vivo organ imaging also showed significant fluorescence signals in tumor tissue. These results indicate that the nanodelivery system of this invention can improve the in vivo delivery process of CyI and enhance its accumulation capacity at the tumor site.

[0020] This invention achieves targeted enrichment of CyI in tumor mitochondria by modifying the PAMAM vector with TPP, thereby improving its subcellular localization ability.

[0021] Cellular colocalization experiments showed that after the CyI-loaded TPP-PAMAM nanosystem entered CT26 tumor cells, its red fluorescence signal significantly overlapped with the mitochondrial green fluorescence signal. Quantitative results showed that the Pearson correlation coefficient between the TPP-modified system and the mitochondrial probe was 0.72, higher than the 0.37 of the unmodified TPP PC system. These results indicate that TPP modification can increase the enrichment of CyI-loaded nanosystems in the mitochondrial region, thereby enhancing the subcellular localization ability of CyI within tumor cells.

[0022] This invention improves the enrichment of photosensitizers in tumor cells, thereby enhancing the targeting and precision of treatment.

[0023] This invention utilizes a combined design of PAMAM nanoloading, nanoparticle delivery, TPP mitochondrial targeting, and CyI near-infrared phototherapy to form a continuous pathway of action: "nanoloading—tumor enrichment—mitochondrial localization—phototherapy output." Related experimental results show that this system can achieve sustained fluorescence enrichment at the tumor site and improve mitochondrial co-localization ability; at 808 nm and 0.96 W / cm²... 2 Under near-infrared light irradiation, a significant singlet oxygen signal can be generated, and the temperature of the TPC system can be increased to 52.6℃. These results indicate that the present invention can make the delivery site and action location of CyI more concentrated, providing a technical basis for improving the targeting and precision of anti-tumor phototherapy. Attached Figure Description

[0024] Figure 1 This is a flowchart of the preparation method of the mitochondrial-targeted nanophotosensitive system with TPP modified PAMAM loaded with Cyl provided in the embodiments of the present invention; Figure 2 This is a schematic diagram illustrating the preparation of the TPP-PAMAM / CyI mitochondrial-targeted nanophotosensitive system provided in this embodiment of the invention; Figure 3 This is a particle size distribution diagram of the nano-photosensitive system provided in the embodiments of the present invention; Figure 4 This is a transmission electron microscope image of the nanophotosensitive system provided in the embodiments of the present invention; Figure 5 This is the UV-Vis absorption spectrum of CyI and its nanosystem provided in the embodiments of the present invention; Figure 6 These are confocal fluorescence images of cell uptake provided in embodiments of the present invention; Figure 7 This is a mitochondrial colocalization analysis diagram provided in an embodiment of the present invention; Figure 8 This is a graph showing the CT26 cell survival rate results provided in an embodiment of the present invention; Figure 9 This is an in vivo fluorescence imaging result image provided in an embodiment of the present invention; Figure 10 These are curves showing the changes in tumor volume in mice under different treatment groups, as provided in this embodiment of the invention. Figure 11 These are comparison images of mouse tumors from different treatment groups provided in this embodiment of the invention. Figure 12 This is a comparison chart of tumor weight in mice with different treatment groups provided in the embodiments of the present invention; Figure 13 This is a flow cytometry result of apoptosis in tumor tissue cells of different treatment groups provided in the embodiments of the present invention. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0026] The mitochondrial-targeted nanophotosensitive system of TPP ((3-carboxypropyl)triphenylphosphine bromide) modified PAMAM (polyamide-amine dendritic polymer) loaded with Cyl (iodoheptamethine cyanine dye) provided in the embodiments of the present invention includes G5 generation PAMAM dendritic macromolecules, triphenylphosphine-based mitochondrial-targeting groups TPP connected to the surface of the G5 generation PAMAM dendritic macromolecules, and near-infrared photosensitizer CyI loaded in the G5 generation PAMAM dendritic macromolecules.

[0027] The TPP provided in this embodiment of the invention is covalently coupled to the surface of the G5 generation PAMAM dendritic macromolecule.

[0028] The TPP provided in this embodiment of the invention is connected to the G5 generation PAMAM dendritic macromolecule via amide bonds.

[0029] The CyI provided in this embodiment of the invention is loaded into the G5 generation PAMAM dendrimer through hydrophobic interaction, electrostatic interaction, or a combination thereof.

[0030] The CyI provided in this embodiment of the invention is loaded into the internal cavity of a TPP-modified G5 generation PAMAM dendritic macromolecule.

[0031] like Figure 1 As shown in the embodiment of the present invention, a method for preparing a mitochondrial-targeted photosensitive nanosystem of TPP-modified PAMAM loaded with Cyl includes the following steps: S101, TPP was coupled with G5 generation PAMAM dendrimer to obtain TPP modified G5 generation PAMAM carrier. S102, CyI is mixed with the TPP-modified G5 generation PAMAM carrier, so that CyI is loaded in the TPP-modified G5 generation PAMAM carrier; S103, the system obtained in step S102 is purified to obtain the mitochondrial-targeted nanophotosensitive system.

[0032] The coupling reaction described in step S101 of the present invention is an amidation reaction based on the surface amino groups of G5 generation PAMAM dendrimers.

[0033] In step S101 of the present invention, TPP is activated with N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride before reacting with G5 generation PAMAM dendrimer.

[0034] The purification process described in step S103 of this embodiment includes one or more of dialysis, centrifugation, ultrafiltration, and freeze drying.

[0035] The application of the mitochondrial-targeted nanophotosensitive system provided in this invention in the preparation of antitumor drugs.

[0036] Example 1: Preparation of TPP-PAMAM carrier Dissolve (3-carboxypropyl)triphenylphosphine bromide in dimethyl sulfoxide, add N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride for activation treatment, wherein the preferred molar ratio of each component is 1:1.5:1.5, and the activation time is 2-4 h.

[0037] Subsequently, G5 generation PAMAM was added, and the reaction was carried out at room temperature in the dark with stirring for 24–48 h, allowing TPP to be attached to the amino groups on the PAMAM surface via an amidation reaction. After the reaction was completed, the mixture was purified by dialysis and freeze-dried to obtain the TPP-PAMAM support.

[0038] Its preparation process is illustrated as follows: Figure 2 As shown.

[0039] Example 2: Preparation of TPP-PAMAM / CyI nanophotosensitive system The TPP-PAMAM obtained in Example 1 was dissolved in deionized water or PBS to obtain a carrier solution; CyI was dissolved in methanol or DMSO (dimethyl sulfoxide).

[0040] CyI solution was added to the carrier solution and stirred at room temperature in the dark for 12–24 h, allowing CyI to be loaded onto the carrier through hydrophobic and electrostatic interactions. Free CyI was then removed by dialysis or centrifugation to obtain the TPP-PAMAM / CyI nanophotosensitive system.

[0041] Example 3 Characterization of the physicochemical properties of the nanosystem The particle size distribution of the nanosystem obtained in Example 2 was determined by dynamic light scattering, and the results are as follows: Figure 3 As shown, the prepared TPP-PAMAM / CyI nanophotosensitive system exhibits a unimodal distribution and a relatively concentrated particle size distribution. Its average hydrated particle size is approximately 90–100 nm, and its polydispersity index (PDI) is approximately 0.20–0.30. These results indicate that the nanosystem possesses good dispersibility and uniformity, which is beneficial for its accumulation at tumor sites in vivo via the EPR effect.

[0042] Its morphology was observed using a transmission electron microscope, such as Figure 4 As shown, the nano-photosensitive system exhibits a regular spherical structure with uniform particle size distribution and no obvious aggregation. The results demonstrate that the constructed nanosystem possesses good structural stability and morphological consistency.

[0043] Its absorption characteristics were detected using ultraviolet-visible absorption spectroscopy, such as... Figure 5 As shown, both free CyI and the TPP-PAMAM / CyI nanosystem exhibit significant absorption peaks in the near-infrared region, and the characteristic absorption peak positions of the nanosystem are basically consistent with those of free CyI, with only slight redshifts or peak shape changes. The results indicate that the molecular structure of CyI was not significantly damaged during loading, and it was successfully encapsulated in the nanosystem.

[0044] Application Example 1: In vitro cell experiments Mouse colon cancer cells CT26 were used as experimental cells. The cells were seeded in 6-well plates at a density of 1 × 10⁶ cells per well. 5 Cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum at 37 ℃ in a 5% CO2 incubator until the cells adhered and grew.

[0045] After discarding the culture medium, the cells were gently washed twice with PBS buffer, and then culture medium containing different treatment systems was added, including: blank control group, free CyI group and TPP-PAMAM / CyI nanophotosensitive system group, in which the final concentration of CyI was 5 μg / mL.

[0046] Cells were incubated in an incubator for 2 h, 4 h, and 8 h, respectively.

[0047] (1) Cell uptake experiment After incubation, the culture medium was discarded, and the cells were washed three times with PBS to remove any nanomaterials that had not entered the cells. The cells were then fixed with 4% paraformaldehyde for 15 min.

[0048] The distribution of intracellular fluorescence was observed using confocal laser scanning microscopy.

[0049] like Figure 6 As shown, the intracellular red fluorescence signal gradually increased under different incubation times (2 h, 4 h, 8 h). Specifically, the intracellular fluorescence was weak at 2 h, significantly increased at 4 h, and reached its strongest level at 8 h, exhibiting a relatively uniform intracellular distribution. These results indicate that the TPP-PAMAM / CyI nanophotosensitive system can be effectively taken up by tumor cells and exhibits time-dependent enhancement.

[0050] (2) Mitochondrial targeting experiment After incubation, Mito-Tracker Green mitochondrial dye (final concentration 100 nM) was added to the cells, and the cells were incubated at 37 °C for 30 min.

[0051] The cells were then washed three times with PBS and observed under a confocal microscope.

[0052] The Pearson correlation coefficient between CyI fluorescence (red) and mitochondrial fluorescence (green) was calculated using image analysis software. A Pearson correlation coefficient of 0.86 indicates a high degree of overlap between CyI fluorescence and mitochondrial signals, suggesting that this nanosystem possesses good mitochondrial targeting capabilities. Figure 7 As shown, the red fluorescence signal of CyI and the green fluorescence signal of the mitochondrial probe show significant overlap within the cell, with a strong yellow signal region appearing in the merged image. Quantitative analysis revealed a Pearson correlation coefficient of over 0.80, indicating a high degree of co-localization between the two. These results demonstrate that the TPP-modified nanophotosensitive system can effectively target and accumulate in the mitochondrial region.

[0053] (3) Cell viability detection CT26 cells were seeded into 96-well plates, approximately 5 × 10⁶ cells per well. 3 Cells were cultured for 24 hours and then added to the three different systems mentioned above. After incubation for 4 hours, they were irradiated with near-infrared laser (808 nm, power density 0.8 W / cm²). 2 , irradiation for 5 minutes).

[0054] After culturing for another 24 hours, CCK-8 reagent was added and incubated for 2 hours. The absorbance was then measured at 450 nm using an ELISA reader.

[0055] like Figure 8 As shown, compared with the control group and the free CyI group, the cell survival rate of the TPP-PAMAM / CyI group was significantly reduced. The cell survival rate of the control group was approximately 100%; the cell survival rate of the free CyI group was approximately 70%–80%; and the cell survival rate of the TPP-PAMAM / CyI group decreased to approximately 20%–30% under near-infrared laser irradiation. These results indicate that the TPP-PAMAM / CyI nanophotosensitive system can significantly inhibit tumor cell activity under near-infrared light irradiation, demonstrating good in vitro antitumor effects.

[0056] Application Example 2: In vivo antitumor experiment Healthy BALB / c mice (female, 6–8 weeks old, weighing approximately 18–22 g) were selected, and CT26 cell suspension (1 × 10⁻⁶) was injected subcutaneously into the right axilla. 6A tumor-bearing mouse model was established using cells per mouse. The tumor volume was increased to approximately 100 mm. 3 Mice were randomly divided into the following groups: control group (Saline); near-infrared irradiation group (NIR); free CyI group (CyI); and TPP-PAMAM / CyI nanophotosensitive system group (TPP-PAMAM / CyI) (n=5 per group).

[0057] (1) In vivo distribution experiment The CyI group and the TPP-PAMAM / CyI group were administered the drug via tail vein injection (CyI dose was 5 mg / kg). In vivo near-infrared fluorescence imaging was performed at 2 h, 6 h, 12 h and 24 h after drug administration.

[0058] like Figure 9 As shown, the fluorescence signal of the TPP-PAMAM / CyI group at the tumor site gradually increased with time, reaching a maximum at 12 h, indicating that the nanosystem has good tumor enrichment ability.

[0059] (2) Anti-tumor therapy experiment Six hours after drug administration, the NIR group, CyI group, and TPP-PAMAM / CyI group were irradiated with near-infrared laser (808 nm, 0.8 W / cm²). 2 The control group received light treatment (irradiated for 5 minutes).

[0060] During the treatment, the tumor volume was measured every 2 days for 14 consecutive days. On the 14th day, as Figure 10 As shown, the tumor volume in the control group increased rapidly over time, reaching approximately 1200 mm on day 14. 3 The tumor volume in the NIR group was approximately 1050–1150 mm. 3 There was no significant difference compared to the control group; tumor growth was somewhat inhibited in the free CyI group, with the tumor volume reaching approximately 800–900 mm on day 14. 3 The TPP-PAMAM / CyI nanosystem group showed significant inhibition of tumor growth, with tumor volume decreasing to approximately 280–350 mm² on day 14. 3 Fifteen days after administration, the tumor tissue was peeled off and removed, as shown in the image. Figure 11 As shown, the tumor volume in the TPP-PAMAM / CyI nanosystem group was significantly smaller than that in other groups. The results indicate that near-infrared irradiation alone has limited inhibitory effect on tumors, while the TPP-PAMAM / CyI nanophotosensitive system can significantly inhibit tumor growth under light irradiation conditions.

[0061] Weigh the dissected and excised tumor tissue and record the tumor weight of mice after different treatments.

[0062] like Figure 12 As shown, the tumor weight in the control group was approximately 1.1–1.3 g; in the NIR group, approximately 1.0–1.2 g; in the free CyI group, approximately 0.7–0.9 g; and in the TPP-PAMAM / CyI nanosystem group, the tumor weight was significantly reduced to approximately 0.2–0.4 g. These results indicate that the described nanophotosensitive system exhibits good in vivo antitumor effects.

[0063] The apoptosis rate of the dissected and excised tumor tissue was detected by flow cytometry.

[0064] like Figure 13 As shown, the apoptosis rate in the control group was approximately 5%–10%; in the NIR group, it was approximately 8%–15%; in the free CyI group, it was approximately 20%–30%; and in the TPP-PAMAM / CyI nanosystem group, the apoptosis rate significantly increased to approximately 55%–70%. These results indicate that the described nanophotosensitive system can significantly induce tumor cell apoptosis.

[0065] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, and improvements made by those skilled in the art within the scope of the technology disclosed in the present invention, and within the spirit and principles of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A mitochondrial-targeted photosensitive nanosystem based on TPP-modified PAMAM loaded with CyI, characterized in that, The nanophotosensitive system includes G5 generation PAMAM dendritic macromolecules, triphenylphosphine (TPP) mitochondrial targeting groups attached to its surface, and near-infrared photosensitizer CyI loaded in the PAMAM.

2. The nanophotosensitive system as described in claim 1, characterized in that, The TPP is covalently coupled to the amino groups on the PAMAM surface, preferably via amide bonds.

3. The nanophotosensitive system as described in claim 1 or 2, characterized in that, The CyI is loaded in the internal cavity, interbranched chain gaps and / or molecular structure of the PAMAM through hydrophobic interactions, electrostatic interactions and / or intermolecular forces.

4. A method for preparing the nanophotosensitive system according to any one of claims 1 to 3, characterized in that, Includes the following steps: (1) TPP was coupled with G5 generation PAMAM dendrimer to obtain TPP-modified G5 generation PAMAM carrier. (2) Mix CyI with the TPP-modified G5 generation PAMAM vector to load CyI in the TPP-modified G5 generation PAMAM vector; (3) The system obtained in step (2) is purified to obtain the mitochondrial-targeted nanophotosensitive system.

5. The preparation method according to claim 4, characterized in that, The coupling reaction described in step (1) is an amidation reaction based on amino groups on the PAMAM surface; preferably, the TPP is activated by N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and then reacts with G5 generation PAMAM dendrimers.

6. The preparation method according to claim 4 or 5, characterized in that, The mixing in step (2) is carried out by stirring in the dark, ultrasound-assisted mixing, or a combination thereof; and / or the purification process in step (3) includes one or more of dialysis, centrifugation, ultrafiltration, gel filtration and freeze drying.

7. The application of the nanophotosensitive system as described in any one of claims 1 to 3 in the preparation of antitumor drugs.

8. The application according to claim 7, characterized in that, The nanophotosensitive system is used for tumor cell uptake and mitochondrial targeted enrichment.

9. The application according to claim 7, characterized in that, The nanophotosensitive system is used to inhibit tumor cell activity and / or induce tumor cell apoptosis under near-infrared light irradiation.

10. The application according to claim 7, characterized in that, The anti-tumor phototherapy drug is used to accumulate in tumor sites in vivo, inhibit tumor growth, and / or induce apoptosis in tumor tissue cells.

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