KR-102962386-B1 - IRIDIUM COMPLEX, PHOTOSENSITIZER AND COMPOSITION FOR PHOTODYNAMIC THERAPY

Abstract

The present invention relates to an iridium complex, a photosensitizer, and a composition for photodynamic therapy. By utilizing a positively charged iridium complex, it exhibits a high accumulation rate within cells and a high reactive oxygen species generation ability, and exhibits not only high cancer cell efficacy compared to existing photosensitizers but also a synergistic effect with conventional iridium complexes.

Inventors

• 권태혁
• 이채규

Assignees

• 울산과학기술원

Dates

Publication Date

20260511

Application Date

20230814

Priority Date

20221017

Claims (8)

1. Iridium complex represented by the following chemical formula 1: [Chemical Formula 1] (Here, R is selected from a methyl group ( CH₃ ) or a trifluoromethyl group ( CF₃ ).)
2. A photosensitizer comprising the iridium complex of claim 1.
3. In paragraph 2, The above photosensitizer is characterized by having a positive charge.
4. A photodynamic composition for cancer treatment comprising the photosensitizer of claim 2 as an active ingredient.
5. A photodynamic composition for cancer treatment according to claim 4, characterized in that the composition is used for the treatment of one or more cancers selected from the group consisting of cervical cancer, colorectal cancer, pancreatic cancer, lung cancer, breast cancer, stomach cancer, melanoma, skin cancer, biliary tract cancer, neuroendocrine tumor, ovarian cancer, liver cancer, bronchial cancer, nasopharyngeal cancer, laryngeal cancer, bladder cancer, colon cancer, brain cancer, prostate cancer, bone cancer, head and neck cancer, thyroid cancer, parathyroid cancer, and ureteral cancer.
6. A photodynamic composition for cancer treatment according to claim 4, characterized in that the composition further comprises one or more selected from the group consisting of a B2 iridium complex represented by the following chemical formula 7 and a TIr3 iridium complex represented by the chemical formula 8: [Chemical Formula 7] [Chemical Formula 8]
7. A photodynamic composition for cancer treatment characterized in that, in claim 6, the composition is for treating cervical cancer.
8. In claim 4, the above composition is a photodynamic composition for cancer treatment characterized by generating active oxygen inside mitochondria upon irradiation with light energy.

Description

Iridium Complex, Photosensitizer and Composition for Photodynamic Therapy The present invention relates to an iridium complex, a photosensitizer, and a composition for photodynamic therapy. By utilizing a positively charged iridium complex, the invention exhibits a high intracellular accumulation rate and a high reactive oxygen species generation ability, and exhibits not only a high cancer cell killing ability compared to existing photosensitizers but also a synergistic effect with existing iridium complexes. Photodynamic therapy is a treatment method that utilizes photochemical reactions to minimize the suffering of cancer patients. It involves administering a photosensitizer to the patient and irradiating the cancer tissue with light; the photosensitizer generates reactive oxygen species through photochemical reactions, which oxidize the biomolecules of cancer cells and cause their death. This treatment method places minimal physical burden on the patient, allowing for retreatment within one month, and can also be combined with existing cancer treatments. However, photosensitizers commonly used in actual photodynamic therapy, such as ' Photofrin ' and 'Radachlorin', have significantly low efficiency in producing reactive oxygen species in aqueous environments, so very strong light energy (> 200~300 J/ cm² ) must be applied for photodynamic therapy. Therefore, iridium complexes, which exhibit very high reactive oxygen species production efficiency in aqueous environments, are being studied as photosensitizers for photodynamic therapy to minimize side effects caused by strong light energy and laser irradiation time; however, improvements are needed regarding the low cell death efficiency and inherent toxicity of iridium complexes. Figure 1 shows the molecular structures of the iridium complexes (HIrb, FIrb) of Examples 1 and 2 and Comparative Examples 1 to 3 (HIra, FIra, FIrp). FIG. 2 is a schematic diagram of the synergistic correlation between the iridium complex combinations of Example 1 (HIrb), Comparative Example 4 (B2), and Comparative Example 5 (TIr3), and the molecular structures of the iridium complexes. Figure 3a is a graph showing the change in intracellular accumulation rate according to the charge of the iridium complex. Figure 3b is an image regarding the merging of the intracellular signal (green) and mitochondrial tracker (red) signal of the iridium complex of Example 1. Figure 4a is a graph showing the change in absorption of 9,10-Anthracenediyl-bis(methylene)dimalonic acid (ABDA) according to the amount of singlet oxygen ( 1 O 2 ) produced according to the light irradiation time. Figure 4b is a graph showing the increase in fluorescence intensity of the Dihydrorhodamine 123 (DHR123) fluorescent substance in response to Type I reactive oxygen species. Figure 4c is an image showing the intracellular fluorescence analysis of 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA, an intracellular Type I reactive oxygen species marker) with and without light irradiation. Figure 5 is a graph showing the synergistic effect with the iridium complexes of Examples 1 and 2 and Comparative Examples 4 and 5. Figure 6 is a graph showing the toxicity of the iridium complex. Figure 7 is a schematic diagram of micellized synergistic combination of TIr3 and B2 and a graph showing the effects thereof. Hereinafter, preferred embodiments of the present invention will be described in more detail with reference to the attached drawings. Prior to this, terms and words used in this specification and claims should not be interpreted as being limited to their ordinary or dictionary meanings, and should be interpreted in a meaning and concept consistent with the technical spirit of the present invention, based on the principle that the inventor can appropriately define the concept of the terms to best describe his invention. Therefore, the embodiments described in this specification and the configurations illustrated in the drawings are merely the most preferred embodiments of the present invention and do not represent all of the technical ideas of the present invention; thus, it should be understood that various equivalents and modifications that can replace them may exist at the time of filing this application. The present invention relates to an iridium complex, a photosensitizer, and a composition for photodynamic therapy. According to one embodiment of the present invention, the iridium complex has cationic properties, has a high accumulation rate within cells, particularly within mitochondria, and can provide a high killing effect on various cancer cells based on high efficiency in generating reactive oxygen species. According to one embodiment of the present invention, the iridium complex may be a compound represented by the following chemical formula 1. [Chemical Formula 1] Here, R can be selected from a methyl group ( CH₃ ) or a trifluoromethyl group ( CF₃ ). The above iridium complex may be selected from the