Photodynamic compounds and methods for activating them using ionizing radiation and/or other electromagnetic radiation for therapy and/or diagnostics
Inventors
Mandel, Arkady • Fisher, Carl • Lilge, Lothar
Assignees
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Publication Number
US-10335608-B2
Publication Date
2019-07-02
Expiration Date
Abstract
A method for destroying cells and/or microorganisms in an organism includes the following steps: (a) administering to the organism a composition including a photodynamic compound containing at least one transition metal; and (b) irradiating the photodynamic compound in the organism with electromagnetic radiation, wherein the electromagnetic radiation includes ionizing radiation and is effective to activate the photodynamic compound to destroy at least one of the cells and the microorganisms in the organism. The ionizing radiation is preferably X-rays and/or gamma rays. The non-ionizing radiation is preferably light in the range from 600-950 nm.
Core Innovation
The invention is directed to a method for destroying cells and/or microorganisms in an organism by administering a composition that includes a photodynamic compound. The photodynamic compound is a metallosupramolecular complex that contains at least one transition metal selected from osmium, manganese, molybdenum, rhenium, ruthenium, iron, cobalt, rhodium, iridium, nickel, platinum, and copper.
After administration, the photodynamic compound is irradiated in the organism with electromagnetic radiation. The electromagnetic radiation comprises X-ray radiation and non-ionizing radiation that are administered in an order and at a power that are synergistically effective to inhibit proliferation of hyperproliferating cells in the organism and/or to destroy microorganisms in the organism.
A related aspect defines gamma rays and non-ionizing radiation to activate the photodynamic compound and destroy at least one of the cells and the microorganisms in the organism. The disclosed embodiments further specify non-ionizing radiation in a wavelength range of 600 to 950 nm and an amount of X-ray radiation in a range of 0.1 to 100 Gy.
Claims Coverage
The provided claim set includes two independent claims. Across these, the inventive coverage centers on a photodynamic metallosupramolecular complex containing selected transition metals and activation by combined ionizing (X-ray or gamma rays) and non-ionizing radiation to inhibit hyperproliferation and/or destroy microorganisms.
Photodynamic metallosupramolecular complex with selected transition metals
A photodynamic compound that is a metallosupramolecular complex containing at least one transition metal selected from osmium, manganese, molybdenum, rhenium, ruthenium, iron, cobalt, rhodium, iridium, nickel, platinum, and copper.
Synergistically effective X-ray and non-ionizing irradiation
Irradiating the photodynamic compound in the organism with electromagnetic radiation comprising X-ray radiation and non-ionizing radiation administered in an order and at a power that are synergistically effective to inhibit proliferation of hyperproliferating cells in the organism and/or destroy microorganisms in the organism.
Gamma rays and non-ionizing radiation to activate photodynamic destruction
Irradiating the photodynamic compound in the organism with gamma rays and non-ionizing radiation effective to activate the photodynamic compound to destroy at least one of the cells and the microorganisms in the organism.
Overall, the independent claims require a photodynamic metallosupramolecular complex with specified transition metals and activation by combining ionizing radiation with non-ionizing radiation. The X-ray-based claim recites synergistically effective order and power for inhibiting hyperproliferation and/or destroying microorganisms.
Stated Advantages
Inhibits proliferation of hyperproliferating cells in the organism.
Destroys microorganisms in the organism.
Synergistically effective activation when X-ray radiation and non-ionizing radiation are administered in an order and at a power.
Destroys at least one of the cells and the microorganisms in the organism by activating the photodynamic compound with gamma rays and non-ionizing radiation.
Accelerated singlet oxygen generation after X-ray irradiation.
Synergistic, non-additive cell kill using X-ray plus red/NIR light.
Improved selectivity and efficacy when photosensitizers are pre-mixed with transferrin.
CT imaging/dosimetry rationale for transition-metal photosensitizers is discussed.
Documented Applications
Destroying cells and/or microorganisms in an organism, including hyperproliferating cells.
In vivo combination use of X-ray with red and/or near infrared light for photodynamic activity, including reported synergistic cell kill in HT1376 and U87 cells.
Delivery-related use with a metal-binding glycoprotein, specifically transferrin, to improve selectivity and efficacy.
CT-based imaging/dosimetry rationale for transition-metal photosensitizers.
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