Metal-glycoprotein complexes and their use as chemotherapeutLots of work going on behind the scene?
Here is full link for your reading pleasure:
https://www.freepatentsonline.com/9737565.html
What a read so here are some excerps from that patent for educational purposes...
"Title:
Metal-glycoprotein complexes and their use as chemotherapeutic compounds
United States Patent 9737565
Abstract:
Compositions of the invention include glycoproteins, such as transferrin, and metal-based coordination complexes, which are preferably chemotherapeutic compounds and more preferably tunable photodynamic compounds. The compositions are useful as in vivo diagnostic agents, and as therapeutic agents for treating or preventing diseases including those that involve hyperproliferating cells in their etiology, such as cancer. Compositions of the invention are further capable of destroying microbial cells, such as bacteria, fungi, and protozoa, and destroying viruses.
Inventors:
Mandel, Arkady (Toronto, CA)
Application Number:
15/000651
Publication Date:
08/22/2017
Assignee:
Theralase Technologies, Inc. (Toronto, CA)
International Classes:
A61K33/24; A61K9/00; A61K38/40; A61K41/00; A61K49/00; A61N5/06
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Download PDF 9737565
"BACKGROUND OF THE INVENTION
1. Field of Invention
This invention relates to metal-based coordination complexes, and more particularly to metal-glycoprotein complexes that are particularly useful as therapeutic and diagnostic agents,
2. Description of Related Art
Photodynamic therapy (PDT) is currently an active area of research for the treatment of diseases associated with hyperproliferating cells such as cancer and non-malignant lesions. The development of new photodynamic compounds (PDCs or photosensitizers, PSs) for photodynamic therapy (PDT) has been increasingly focused on metallosupramolecular complexes derived from metals. For example, WO 2013158550 A1 and WO 2014145428 A2 disclose metal-based PDCs useful as in vivo diagnostic agents, as therapeutic agents for treating or preventing diseases that involve unwanted and/or hyperproliferating cell etiology, including cancer, as agents for treating infectious diseases, and as agents for pathogen disinfection and/or sterilization. U.S. Pat. No. 6,962,910, U.S. Pat. No. 7,612,057, U.S. Pat. No. 8,445,475 and U.S. Pat. No. 8,148,360 disclose supramolecular metal complexes capable of cleaving DNA when irradiated low energy visible light with or without molecular oxygen.
Delivery of metal-based coordination complexes and PDCs to biological targets can pose a challenge, which many have attempted to address.
For example, US 20120264802 discloses photosensitizer compounds based on functionalized fullerenes useful in targeted PDT, and methods of use thereof.WO 2013020204 A1 discloses biodegradable polymeric nanoparticles comprising an inner core formed of a photodynamic agent capable of being activated to generate cytotoxic singlet oxygen. These nanoparticles have anti-cell proliferation activity and are useful in treating both cancerous and non-cancerous conditions including actinic keratosis, psoriasis and acne vulgaris. Preferably, the photodynamic agent is a hypocrellin B derivative while the polymeric nanoparticle comprises polyglycolic acid, polylactic acid or poly(lactide-co-glycolide). Hypocrellin-comprising nanoparticles are demonstrated to be activated by light or hydrogen peroxide"
"BRIEF SUMMARY OF THE INVENTION
A first aspect of the invention comprises a composition comprising: a metal-binding glycoprotein; and a chemotherapeutic compound containing at least one transition metal preferably selected from the group consisting of Ru, Rh and Os, wherein the composition has at least one of the following enhanced properties relative to the chemotherapeutic compound without the glycoprotein: (a) increased uptake by cancer cells; (b) increased uptake by tumors; (c) increased efficacy at wavelengths longer than 600 nm; (d) increased efficacy at wavelengths less than or equal to 600 nm; (e) improved absorbance at wavelengths longer than 600 nm; (f) improved absorbance at wavelengths less than or equal to 600 nm; (g) increased production of reactive oxygen species; (h) increased photodynamic therapy effect under non-hypoxic conditions; (i) increased photodynamic therapy effect under hypoxic conditions; (j) increased LD50; (k) increased MTD; (l) increased photostability; and (m) increased shelf-life."
"A second aspect of the invention comprises a method for treating a condition associated with hyperproliferating cells, said method comprising:administering to a subject having the condition an effective amount of the composition according to the invention; and irradiating the subject with light effective to activate the composition so as to treat the condition."
"A third aspect of the invention comprises a method for destroying a microbial cell, said method comprising: contacting the microbial cell with an effective amount of the composition according to the invention; and irradiating the microbial cell with light effective to activate the composition so as to destroy the microbial cell."
"Advantages of the Invention
The invention is based in part on the
unexpected discovery that Ru, Rh and Os based PDCs, particularly those disclosed in WO 2013158550 A1, WO 2014145428 A2, U.S. Pat. No. 6,962,910, U.S. Pat. No. 7,612,057, U.S. Pat. No. 8,445,475 and U.S. Pat. No. 8,148,360, are significantly improved in their chemical, physical and biomedical properties when they are administered in combination with metal-binding glycoproteins of the invention"
"During light activation in preferred embodiments of the invention, in addition to PDT-induced inflammation, there is modification of tumor cell death and antigen presenting cells (“APC”) activation via the danger-associated molecular patterns (“DAMPs”). The recognition of molecules released or expressed by dead, dying, injured, or stressed “antigenic”-apoptotic cells can elicit potent and tumor-specific immune responses. PDT-induced DAMPs emitted by dying cancer cells can elicit cancer antigen-directed anti-tumor short-term effects (6 to 8 weeks) and a long-term anti-tumor effect (>10 months) immunity. DAMP's stimulate immune responses through dialogue with T lymphocytes (“Th”) cells, Natural Killer (“NK”) cells and APSs. Certain APSs, such as dendritic cells and macrophages are stimulated and actively trafficked during PDT-induced “immunologic” cell death (“ICD”) by danger signalling pathways, which are instigated and regulated by a complex interplay between cellular stress signaling, reactive oxygen species (“ROS”) production and certain metabolic/biosynthetic processes (i.e., autophagy, caspase activity and secretory pathway: calreticulin, Adenosine Tri-Phosphate (“ATP”), Heat Shock Proteins, High Mobility Group Box 1, cytokines, etc)."
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