A photoresponsive ion pair composition and its anticancer application

Abstract

The present invention belongs to the field of medicinal chemistry and specifically discloses a light-responsive ion pair composition and its anti-cancer application. The ion pair composition includes a cyclometallic gold (III) complex and a photosensitizer, wherein the photosensitizer includes eosin (EY) or rose bengal (RB), and the structural formula of the cyclometallic gold (III) complex is shown in formula (1). The composition modifies the structure of the known cyclometallic gold (III) complex skeleton by adding hydroxyl groups, morpholine rings and deuteration, thereby improving its water solubility, charge properties, stability and other aspects. It can be efficiently activated by green light or even red light and has anti-cancer applications. The present invention achieves efficient activation of the cyclometallic gold (III) complex by combining the cyclometallic gold (III) complex with eosin (EY) or rose bengal (RB), and can extend the excitation wavelength to the red light range; and based on the ion pair properties and the characteristics of the tumor microenvironment, tumor-specific treatment can be achieved more accurately on the basis of light irradiation.

Description

Technical Field

[0001] The present invention belongs to the field of medicinal chemistry, and in particular relates to a light-responsive ion pair composition and its anti-cancer application. Background Art

[0002] Gold (III) and gold (I) complexes have been reported as anticancer drugs for various cancers, exhibiting excellent antiproliferative activity against a variety of cancer cells, including those resistant to cisplatin. However, due to the high affinity of Au for S or Se, these gold (III) and gold (I) complexes selectively target proteins and enzymes containing thiol (cysteine) or selenol (selenocysteine) structures. This results in gold (III) and gold (I) complexes not only selectively inhibiting thiol / selenol-containing enzymes (e.g., thioredoxin reductase, TrxR) but also potentially binding to thiol compounds in non-tumor sites, leading to off-target effects. Therefore, there is an urgent need to develop new drugs and methods to modulate the reactivity of gold towards thiols.

[0003] Photoreactive cyclometallated gold(III) complexes have been reported as prodrugs. They are virtually nontoxic to cells in the dark, but exhibit strong antiproliferative effects upon illumination, thus achieving the goal of controllable activation of gold anticancer drugs. However, activation is currently only possible with ultraviolet or blue light. These shorter wavelength light sources suffer from insufficient penetration, are prone to tissue damage, and cannot accurately distinguish between tumor tissue and normal areas.

[0004] Therefore, there is an urgent need to develop a cyclometalated gold (III) complex that can be activated by long-wavelength light, and on this basis, to improve the activation efficiency and further achieve selectivity between tumor cells and normal cells. Summary of the Invention

[0005] The present invention aims to address at least one of the technical problems existing in the aforementioned prior art. To this end, the present invention provides a light-responsive ion pair composition and its anticancer application. The ion pair composition, comprising a cyclometallated gold(III) complex and the photosensitizers eosin (EY) or rose bengal (RB), can be efficiently activated by green or even red light and exhibits anticancer effects.

[0006] To solve the above technical problems, the first aspect of the present invention provides an ion pair composition comprising a cyclometalated gold (III) complex and a photosensitizer, wherein the photosensitizer comprises eosin (EY) or rose bengal (RB), and the structural formula of the cyclometalated gold (III) complex is shown in formula (1):

[0007]

[0008] Where: R 1 Indicates H or D; R 2 Indicates H, CH2OH, Any one of .

[0009] Specifically, the present invention modifies the skeleton of a cyclometalated gold(III) complex by adding hydroxyl groups, morpholine rings, and deuteration, thereby improving its water solubility, charge properties, and stability. Under physiological conditions, the cyclometalated gold(III) complex with the morpholine ring is protonated and positively charged, while the carboxyl-containing photosensitizers eosin (EY) or rose bengal (RB) are deprotonated and negatively charged, forming an ion-pair complex.

[0010] At the same time, the cyclometallated gold(III) complex, as an active gold prodrug, possesses a certain degree of stability and is activated and released upon illumination. The photosensitizers eosin (EY) or rose bengal (RB), as light-sensitive compounds, strongly absorb in the green light (530nm) range and become excited upon illumination, thereby catalyzing the photoredox reaction of the substrate. By combining the cyclometallated gold(III) complex with the photosensitizers eosin (EY) or rose bengal (RB), efficient activation of the cyclometallated gold(III) complex can be achieved, and the excitation wavelength can be extended to the red light range by red-shifting the absorption range of the photosensitizer through interaction.

[0011] As a further improvement of the above scheme, the cyclometalated gold (III) complex is selected from one of the following structural formulas:

[0012]

[0013] As a further improvement of the above scheme, the structural formulas of eosin (EY) and rose bengal (RB) are shown in formula (3) and formula (4), respectively:

[0014]

[0015] As a further improvement of the above scheme, the molar ratio of the cyclometalated gold (III) complex and the photosensitizer is 1:1-10:1.

[0016] The second aspect of the present invention provides a method for activating the ion pair composition, wherein the ion pair composition is activated by light irradiation, and the light source of the light irradiation is green light or red light.

[0017] As a further improvement of the above solution, the wavelength of the light source is 530-630 nm.

[0018] Specifically, because the absorption range of cyclometallic gold (III) complexes is roughly 250-450 nm, methods for activating the compound through light irradiation are limited to shorter-wavelength ultraviolet or blue light, which cannot achieve deep tissue penetration. The present invention indirectly activates the cyclometallic gold (III) complex by adding the photosensitizer eosin (EY) or rose bengal (RB) to the cyclometallic gold (III) complex and irradiating the cyclometallic gold (III) complex with the photosensitizer's own absorbed light (530 nm). Under 530 nm light irradiation, the photosensitizer eosin (EY) or rose bengal (RB) becomes excited and rapidly reacts with the cyclometallic gold (III) complex, thereby activating the cyclometallic gold (III) complex prodrug and releasing active gold.

[0019] At the same time, the cyclometalated gold (III) complex of the present invention forms an ion pair with the photosensitizer eosin (EY) or rose bengal (RB), shortening the distance between molecules and improving the reaction efficiency. Compared with ultraviolet or blue light irradiation, the reaction is more efficient and rapid.

[0020] In addition, the interaction between molecules can not only shorten the distance between molecules, but also cause certain changes in the optical properties of the photosensitizer eosin (EY) or rose bengal (RB), resulting in a red shift in the absorption of light. Therefore, selecting a light source with a longer wavelength (600-630nm) to irradiate it can also achieve the activation of the cyclometallic gold (III) complex. At the same time, red light irradiation of the cyclometallic gold (III) complex-photosensitizer eosin (EY) ion pair composition can not only avoid the toxicity caused by the generation of reactive oxygen species (ROS) by the irradiated photosensitizer itself, but also achieve higher tissue permeability, providing a way to achieve the treatment of deep tissue tumors.

[0021] The third aspect of the present invention provides the use of the ion pair composition in the preparation of anticancer drugs.

[0022] As a further improvement of the above scheme, the anti-cancer effect includes selectively inhibiting cancer cell proliferation and / or inhibiting angiogenesis.

[0023] As a further improvement of the above solution, the cancer cells include any one of lung cancer cells, colon cancer cells, and liver cancer cells.

[0024] As a further improvement of the above solution, the pH value of the anti-cancer microenvironment is 5.5-7.0.

[0025] Specifically, the ion pair composition of the present invention can achieve selective inhibition that distinguishes cancer cells from normal cells based on pH. Based on the characteristics of the tumor microenvironment, its pH range is 5.5-7.0. Therefore, compared with 7.4 of normal tissue, the pH of the tumor site is significantly reduced. Since the pKa of the photosensitizer eosin (EY) or rose bengal (RB) is about 2-3, it is easily deprotonated in a physiological environment, and the molecule always exists in a negatively charged form; while the pKa of the morpholine ring is higher, compared with the environment of normal tissue pH = 7.4, it is easier to achieve protonation in the slightly acidic environment of tumor tissue, forming a higher proportion of positively charged amines, thereby forming more ion pairs with the negatively charged photosensitizer eosin (EY), promoting the red shift of the light absorption of eosin (EY). At this time, irradiation with red light (600-630nm) can produce more active gold in the tumor site where more ion pairs are formed, thereby achieving the purpose of being non-toxic or less toxic to normal tissues and more toxic to tumor tissues.

[0026] Compared with the prior art, the above technical solution of the present invention has at least the following technical effects or advantages:

[0027] The cyclometalated gold (III) complex-photosensitizer eosin (EY) / rose bengal (RB) ion pair composition of the present invention has the performance of responding to green light and red light. On the basis that the existing technology can only be activated by ultraviolet-blue light, it further achieves a breakthrough in the red shift of excitation light. Under green light irradiation, the cyclometalated gold (III) complex prodrug can be activated and targeted to thiol compounds. Under red light irradiation, the cyclometalated gold (III) complex and the photosensitizer eosin (EY) or rose bengal (RB) alone have no effect, but the ion pair composition composed of the two compounds can achieve light response due to their characteristics, and produce and release active gold. In addition, through light-controlled selective irradiation, and based on the characteristics of the ion pair composition and the tumor microenvironment in the present invention, the selectivity for tumor tissue is comprehensively improved. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 The stability comparison chart of cyclometalated gold (III) complex (1a) and its deuterated complex (2a);

[0029] Figure 2 The figure is a comparison of the stability of cyclometalated gold (III) complex (1a) and its deuterated complex (2a) to thiol groups at 37°C;

[0030] Figure 3 is the HPLC trace spectrum of the ion pair composition after irradiation;

[0031] Figure 4 The UV-Vis spectrum of the ion pair composition after irradiation and the reaction rate comparison diagram thereof;

[0032] Figure 5The characterization diagram of the ion pair formed by the cyclometalated gold (III) complex and the photosensitizer eosin (EY) or rose bengal (RB);

[0033] Figure 6 A comparison diagram of blood vessel formation during zebrafish embryonic development;

[0034] Figure 7 The figure shows the selective activation of ion pair compositions based on pH. DETAILED DESCRIPTION

[0035] The present invention is described in detail below with reference to the examples to facilitate understanding of the present invention by those skilled in the art. It is necessary to point out that the examples are only used to further illustrate the present invention and are not to be construed as limiting the scope of protection of the present invention. Non-essential improvements and adjustments made to the present invention by those skilled in the art based on the above-mentioned invention should still fall within the scope of protection of the present invention. At the same time, the raw materials mentioned below that are not described in detail are all commercially available products; the process steps or preparation methods that are not mentioned in detail are all process steps or preparation methods known to those skilled in the art.

[0036] Example 1: Characterization of cyclometallated gold (III) complexes

[0037] The cyclometallated gold (III) complexes 1a-1d and 2a-2d of the present invention were prepared with reference to the method for preparing photoresponsive cyclometallated gold (III) hydrides disclosed in the applicant's prior patent application (Publication No.: CN 111004259 A). The structures, H NMR spectra, and C NMR spectra of cyclometallated gold (III) complexes 1a-1d are shown in Table 1. The H NMR and C NMR spectra of cyclometallated gold (III) complexes 2a-2d are essentially identical to those of the corresponding hydrides 1a-1d, except for the absence of the negative hydrogen peak at a chemical shift of approximately -6.5, which is not further described here.

[0038] Table 1: Characterization data of cyclometallated gold (III) complexes 1a-1d

[0039]

[0040] Example 2: Comparison of the Stabilities of Cyclometalated Gold(III) Complexes and Their Deuterated Complexes

[0041] The stability of the cyclometallic gold (III) complex (1a) and its deuterated complex (2a) at room temperature was tested. The specific test process was as follows: 10 mM cyclometallic gold (III) complex (1a) and cyclometallic gold (III) complex (2a) were dissolved in deuterated chloroform (CDCl3) respectively, and placed in a dark place for 72 hours. During the static process, samples were taken every 24 hours for nuclear magnetic resonance detection. The test results are as follows: Figure 1 shown.

[0042] from Figure 1 It can be seen that the changes in the NMR spectrum of the cyclometallic gold (III) complex (2a) after being placed at room temperature for 72 hours are significantly slower than those of the cyclometallic gold (III) complex (1a), indicating that the stability of the cyclometallic gold (III) deuterated complex at room temperature is higher than that of the cyclometallic gold (III) hydride.

[0043] Example 3: Comparison of the Stability of Cyclometalated Gold(III) Complexes and Their Deuterated Complexes to Sulfhydryl Groups at 37°C

[0044] The stability of cyclometalated gold (III) complex (1a) and its deuterated complex (2a) to sulfhydryl groups at 37°C was tested. The specific test process was as follows: 100 μM cyclometalated gold (III) complex (1a) and cyclometalated gold (III) complex (2a) were mixed with 10 mM N-acetylcysteine ​​(NAC) in dimethyl sulfoxide-d6 (DMSO-d6), and placed in the dark for 72 hours. During the static process, samples were taken every 24 hours for nuclear magnetic resonance detection. The results are as follows: Figure 2 shown.

[0045] from Figure 2 It can be seen that the stability of cyclometallated gold(III) deuterated complexes is greater than that of cyclometallated gold(III) hydride, whether at room temperature or at 37°C in the presence of NAC.

[0046] Example 4: Comparison of photoreaction rates of ion pair compositions under green light and ultraviolet light

[0047] 100 μM cyclometalated gold (III) complex (1d) was added to a mixed solvent of 90% DMSO + 10% H2O with 10 mM N-acetylcysteine ​​(NAC), 10 mM NaOH and 10 μM eosin (EY). The mixture was irradiated with green light (530 nm). The absorption spectrum was recorded every 5-10 s from the start of irradiation. The absorption spectrum was followed by detection using ultraviolet-visible spectrophotometry (UV-Vis) and high performance liquid chromatography (HPLC). The test results were as follows: Figure 3 and Figure 4 As shown in B.

[0048] 100 μM cyclometalated gold (III) complex (1d), 10 mM N-acetylcysteine ​​(NAC) and 10 mM NaOH were added to a mixed solvent of 90% DMSO + 10% H2O and irradiated with ultraviolet light (365 nm). The absorption spectrum was recorded every 20 s from the start of irradiation and tracked by UV-Vis. The test results are shown in Figure 2. Figure 4 As shown in A.

[0049] Draw a graph with time as the horizontal axis and the optical density (OD) absorption change (Relative change of Abs) as the vertical axis, such as Figure 4 As shown in C. Figure 4 As shown in Figure C, the activation of the cyclometallated gold(III) complex by eosin (EY) reaches a plateau in approximately 20 seconds, whereas it takes 180 seconds or even longer under UV irradiation. This phenomenon indicates that the photoreaction efficiency of the photosensitizer eosin (EY) is much higher than that of direct UV irradiation. This is likely due to the high photoredox activity of eosin and the formation of an ion-pair complex between the positively charged cyclometallated gold(III) complex and the negatively charged photosensitizer eosin (EY), which greatly increases intermolecular collisions and contacts.

[0050] Example 5: Characterization of the ion-pair interaction between cyclometallated gold (III) complexes and photosensitizers eosin (EY) or rose bengal (RB)

[0051] (1) 20 μM photosensitizer eosin (EY) and 20 μM, 40 μM, 60 μM, 80 μM, and 100 μM cyclometalated gold (III) complex (1d) were added to a mixed solvent of 10% DMSO + 90% H2O, and the absorption spectra were recorded and photographed. The results are shown in the figure. Figure 5 A, as shown in 5E.

[0052] (2) 20 μM photosensitizer eosin (EY) was added to a mixed solvent of 10% DMSO + 90% H2O with 20 μM, 40 μM, 60 μM, 80 μM, and 100 μM NaOH, and the absorption spectra were recorded. The results are as follows: Figure 5 As shown in B.

[0053] (3) 20 μM photosensitizer Rose Bengal (RB) and 20 μM, 40 μM, 60 μM, 80 μM, and 100 μM cyclometalated gold (III) complex (1d) were added to a mixed solvent of 10% DMSO + 90% H2O, and the absorption spectra were recorded and photographed. The results are shown in Figure 2. Figure 5 As shown in C.

[0054] (4) 20 μM of the control cyclometalated gold (III) complexes (1a), (1b) and (1d) were added to a mixed solvent of 10% DMSO + 90% H2O with 20 μM of the photosensitizer Eosin (EY), and the absorption spectra were recorded. The results are shown in Figure 4. Figure 5 As shown in D.

[0055] (5) 10 mM cyclometalated gold (III) complex (1d), 10 mM photosensitizer eosin (EY), and 10 mM compound 1d + 10 mM photosensitizer eosin (EY) were dissolved in DMSO-d6 and subjected to NMR detection. The results were as follows: Figure 5After assigning the peaks, we can know the NMR signals corresponding to each hydrogen, as shown in Figure 5 As shown in G.

[0056] from Figure 5 It can be seen that cyclometalated gold(III) complexes with morpholine ring structures have a significant interaction with the photosensitizer Eosin (EY). UV-Vis spectra show a significant red shift in the maximum absorption peaks of Eosin (EY) and Rose Bengal (RB), and the color change is visible to the naked eye. Nuclear magnetic resonance also shows that chemical shifts of some peaks change after direct mixing of cyclometalated gold(III) complexes with Eosin (EY). In contrast, cyclometalated gold(III) complexes without morpholine rings do not change the maximum absorption peak of Eosin (EY), and the influence of pH changes on their absorption peaks is eliminated. After assigning each hydrogen, analysis showed that the chemical shifts of hydrogens at positions e and d on the cyclometalated gold (III) complex 1d with a morpholine ring structure changed, while a', b', c', and e' in the structure of the photosensitizer eosin (EY) also underwent chemical shifts or changes in peak shape, while the remaining peaks remained unchanged, indicating that some hydrogens in the two molecules can affect each other, indicating that the cyclometalated gold (III) complex 1d with a morpholine ring structure has intermolecular interaction with the photosensitizer eosin (EY).

[0057] Example 6: Inhibitory effect of cyclometalated gold (III) complexes combined with photosensitizer eosin (EY) on cancer cells

[0058] (1) Seed cells

[0059] Discard the original culture medium, wash three times with 2 mL of PBS, digest with 1 mL of trypsin for 30 s, add 2 mL of culture medium to terminate the digestion, transfer to a centrifuge tube, centrifuge at 1000 rpm for 3 min, discard the supernatant, add 2 mL of culture medium and pipette 10 times to mix, take 10 μL of cell suspension to a cell counter and count; spread 96-well plates, seed 5000 cells per well, calculate the required cell amount and cell well amount for 3 replicates for each compound, calculate the required cell suspension amount by cell counting, dilute the required number of cells with culture medium, spread 100 μL of culture medium per well with 5000 cells, mix by pipetting, seed the cells with a spray gun, place in an incubator for culture, and mark them.

[0060] (2) Dosing

[0061] Discard the original culture medium and dilute the cyclometalated gold (III) complex (1c) stock solution with a culture medium containing a certain concentration of photosensitizer eosin (EY) to final concentrations of 0, 0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 μM, respectively. Mix well and use a dispenser (use 3 of the wells) to aspirate 100 μL of dilution into each well. Tilt the 96-well plate and add the dilution to the corresponding 3 marked wells (to prevent cells from being injured). Add each concentration of dilution in turn, pipette and pipette about 3 times to mix, and repeat this process for each compound. Mark the plate, shake it gently 3 times, and place it in a CO2 incubator.

[0062] (3) Light

[0063] One hour after drug addition, the 96-well plates of the experimental group that needed illumination were placed on a cell phototoxicity instrument for illumination at 530 nm for 5 min. After illumination, the plates were returned to the incubator for continued cultivation.

[0064] (4) MTT colorimetry

[0065] After the drug acted on the cells for 48 hours, 20 μL of MTT was added to each well of a 96-well plate using a dispenser (MTT concentration was 5 mg / mL in PBS); the plates were incubated at 37°C for 4 hours. After the incubation time was over, the MTT mixture was aspirated and DMSO was added at 130 μL / well using a dispenser; the plates were shaken on a horizontal shaker for 10 minutes until the formazan was fully dissolved, and the absorbance was measured at a wavelength of 490 nm using a microplate reader. The cell survival rate at each drug concentration was calculated as required, and a scatter plot was made to obtain the IC values ​​of each cyclometallated gold (III) complex (1c) on cancer cell proliferation. 50 , the results are shown in Table 2.

[0066] Table 2: Inhibitory activity of cyclometallated gold (III) complex (1c) combined with photosensitizer eosin (EY) against cancer cells

[0067]

[0068] As shown in Table 2, the cyclometalated gold (III) complex (1c) was non-toxic to A549 human lung cancer cells, HCT116 human colon cancer cells, and PC9 human lung cancer cells under dark conditions, but exhibited excellent inhibitory effects under green light illumination.

[0069] Example 7: Inhibitory effect of cyclometalated gold (III) complexes combined with photosensitizer eosin (EY) on cancer cells

[0070] 100 μM of cyclometallated gold(III) complex (1d) and 100 μM of photosensitizer Eosin (EY) were dissolved in zebrafish culture water. Embryos were treated with the drug-containing aqueous solution for 1 hour and then irradiated with 600 nm light for 30 minutes. Four days later, zebrafish were photographed using an inverted fluorescence microscope. Damage to the caudal artery (CA) and intersegmental vessels (IV) was observed in the treated groups, along with a loss of dorsal longitudinal anastomotic vessels (DLAVs), particularly in the tail. For comparison, embryos treated with only 100 μM of cyclometallated gold(III) complex (1d), only 100 μM of photosensitizer Eosin (EY), or a drug-free aqueous solution showed no significant inhibitory effect.

[0071] Figure 4: Blood vessel formation during zebrafish embryonic development Figure 6 As shown, from Figure 6 As can be seen, zebrafish blood vessels in the drug-treated and light-exposed group were inhibited, while blood vessel growth in the control group under the same conditions was normal. This experiment demonstrates that the ion-pair composition of the present invention can be activated by red light in vivo and inhibit angiogenesis in zebrafish. When applied to tumor sites, it inhibits angiogenesis within the tumor after light activation, reducing energy supply and thus has the potential to inhibit tumor growth.

[0072] Example 8: pH-dependent selective activation of cyclometallated gold (III) complex-photosensitizer eosin (EY) ion pair compositions

[0073] (1) 50 μM cyclometalated gold (III) complex (1d), 50 μM photosensitizer eosin (EY) and 0.1 M NaCl were added to a mixed solvent of 10% DMSO + 90% H2O at different pH values, and the absorption spectra were recorded, as shown in Figure 2. Figure 7 As shown in A.

[0074] (2) With pH as the horizontal axis and the absorbance at 600 nm as the vertical axis, draw a graph, as shown in the following example: Figure 7 As shown in B.

[0075] (3) 100 μM of cyclometalated gold (III) complex (1d) and 100 μM of photosensitizer eosin (EY) were added to a mixed solvent of 10% DMSO + 90% H2O at pH 5.5 and 7.4, respectively, and the absorption spectra were recorded. Figure 7 As shown in C.

[0076] (4) The two pH systems in step (3) were illuminated with 600 nm light for 60 min, filtered with a 0.22 μM filter, and the supernatant was diluted five times with bacterial culture medium LB and transferred to E. coli carrying pGolS-mCherry cultured overnight. After incubation for 11 h, the fluorescence intensity was measured. Figure 7 As shown in D.

[0077] (5) First, adjust the pH of the empty culture medium to 5.5 and 7.4, add cells, and then mix the DMSO concentrated solution of the cyclometallic gold (III) complex (1d) and the photosensitizer eosin (EY), add them to the two pH systems, dilute them to final concentrations of 0, 0.78125, 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 μM, and mix them evenly. Irradiate with 600 nm light for 60 minutes, then immediately wash off the culture medium and replace it with a drug-free empty culture medium. After the drug acts on the cells for 24 hours, the IC values ​​of the cyclometallic gold (III) complex (1d) combined with eosin (EY) on cancer cell proliferation under different pH and red light irradiation are obtained by MTT colorimetry. 50 ,like Figure 7 As shown in E.

[0078] from Figure 7 As can be seen in the figure, after the photosensitizer Eosin (EY) forms an ion pair with the cyclometallated gold (III) complex, a distinct new peak is generated at 561 nm. The absorption at pH 5.5 is significantly stronger than that at pH 7.4. However, the new peak at 561 nm gradually decreases regardless of whether the pH is increased or decreased. This is because as the solution becomes more alkaline, the protonated cyclometallated gold (III) complex decreases, forming fewer ion pairs with the photosensitizer Eosin (EY). Conversely, as the solution becomes more acidic, the structure of the photosensitizer Eosin (EY) itself may be destroyed, resulting in a decrease in overall absorption.

[0079] The ion pairs were activated under both the tumor microenvironment pH of 5.5 and the physiological environment pH of 7.4, and characterized using E. coli carrying pGolS-mCherry. After a certain period of time, the expression of the mCherry fluorescent protein was measured, and significant differences were observed. This indicates that the pH of 5.5 system produces significantly more active gold than the pH of 7.4 system. Similarly, in the cell environment of pH 5.5, the ion pairs are more activated, resulting in stronger cytotoxicity.

[0080] For those skilled in the art to which the present invention belongs, a number of simple deductions or substitutions can be made without departing from the concept of the present invention, without having to resort to creative work. Therefore, based on the disclosure of the present invention, simple improvements made by those skilled in the art to the present invention should be within the scope of protection of the present invention. The above embodiments are preferred embodiments of the present invention, and all processes similar to the present invention and equivalent changes made should fall within the scope of protection of the present invention.

Claims

1. An ion pair composition, characterized in that The invention comprises a cyclometalated gold (III) complex and a photosensitizer, wherein the photosensitizer comprises eosin or rose bengal, and the structural formula of the cyclometalated gold (III) complex is shown in formula (1): Where: R 1 Indicates D; R 2 express 、 Any of the following; The structural formulas of eosin and rose bengal are shown in formula (3) and formula (4), respectively: The ion pair composition is activated by green light or red light.

2. The ion pair composition according to claim 1, characterized in that The molar ratio of the cyclometalated gold (III) complex to the photosensitizer is 1:1-10:

1.

3. The ionic composition according to claim 1, characterized in that The wavelength of the activated light source is 530-630 nm.

4. Use of the ion pair composition according to any one of claims 1 to 3 in the preparation of anticancer drugs.

5. The use according to claim 4, characterized in that The anti-cancer effect includes selectively inhibiting cancer cell proliferation and / or inhibiting angiogenesis.

6. The use according to claim 5, characterized in that The cancer cells include any one of lung cancer cells, colon cancer cells, and liver cancer cells.

7. The use according to claim 4, characterized in that The pH value of the anti-cancer microenvironment is 5.5-7.0.

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