Photo-controlled removal of targets in vitro and in vivo
Inventors
Kobayashi, Hisataka • Choyke, Peter • Schnermann, Martin John
Assignees
US Department of Health and Human Services
Publication Number
US-10830678-B2
Publication Date
2020-11-10
Expiration Date
2035-08-07
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Abstract
This disclosure provides IR700-molecule conjugates and methods of their use to remove (e.g., separate or isolate) a target from a sample in vivo or from a subject in vitro. It is shown herein that exposure of IR700 to near infrared (NIR) light removes a portion of IR700, changing it from a hydrophilic molecule, to one that is hydrophobic, resulting in aggregation of IR700 and anything bound to it. For example, the disclosed IR700-molecule conjugates and methods provide photo-controlled ways to control the pharmacokinetics of a drug in vivo, and can be used to remove undesired agents from environmental or food samples or to isolate target molecules in a laboratory.
Core Innovation
This disclosure provides IR700-molecule conjugates and methods for using near infrared (NIR) light exposure to remove, separate, or isolate a target from a sample in vitro or from a subject in vivo. Upon exposure to NIR light, a portion of IR700 is cleaved, converting it from a hydrophilic to a hydrophobic molecule and causing aggregation of IR700 and anything bound to it. The IR700 dye is conjugated to specific binding agents (e.g., antibodies, antibody fragments, haptens, proteins, nucleic acids, functional nucleic acids) or pharmacological agents, enabling precise labeling of target molecules through binding.
The disclosed methods use photo-controlled ways to regulate the pharmacokinetics of a drug in vivo, remove undesired agents from environmental or food samples, or isolate target molecules in laboratory settings. By irradiating IR700-molecule conjugate-target complexes with NIR light, the conjugates become hydrophobic and aggregate, facilitating their removal by precipitation or by biological clearance mechanisms such as uptake by the liver or spleen.
The problem addressed arises from the difficulty in modifying, isolating, or eliminating a particular biomolecule among complex mixtures in solutions, cells, or whole organisms using current technologies. Conventional approaches struggle with selective removal or isolation of specific proteins or target molecules in complex environments. The present invention introduces a method to overcome such challenges by harnessing IR700 conjugates and NIR light-induced hydrophobic aggregation to separate and remove targets efficiently.
Claims Coverage
The patent contains two independent claims focused on methods for controlling pharmacokinetics of molecules and removing pathogens from subjects. The main inventive features involve use of IR700 conjugates, NIR irradiation conditions, and aggregation-based removal of targets.
Method for controlling pharmacokinetics of IR700-conjugated molecules
Administering a therapeutically effective amount of an IR700 conjugate bound to a molecule such as proteins, peptides, lectins, carbohydrates, metals, nucleic acid molecules, small organic molecules, or pharmacological agents. Subsequent irradiation of the subject with NIR light at 660-710 nm and at doses sufficient to cleave IR700, facilitating formation of a hydrophobic IR700-molecule, which aggregates, traffics to liver and/or spleen, and is excreted. Detection of the aggregate in urine or bowel movements controls the molecule's pharmacokinetics.
Method for removing a pathogen using IR700 conjugated to specific binding agents
Administering an IR700 conjugated specific binding agent that binds the pathogen; allowing binding; irradiating the subject with NIR light (660-710 nm) to cleave IR700 and generate hydrophobic IR700-specific binding agent-pathogen complexes; allowing aggregation of these complexes in the subject; and excreting the aggregates from the subject.
The claims cover methods of in vivo removal of target molecules or pathogens using IR700-molecule conjugates activated by NIR light to induce hydrophobic aggregation and subsequent removal, enabling controlled pharmacokinetics or pathogen clearance.
Stated Advantages
Provides photo-controlled ways to regulate pharmacokinetics of drugs in vivo.
Enables selective removal or isolation of molecular targets from complex biological, environmental, or food samples.
Allows removal of unwanted agents, including toxins, pathogens, metals, and cells, in vivo or in vitro.
Methods permit targeted cell killing with minimal damage to non-target cells, enhancing specificity of treatment.
IR700 dye maintains fluorescence after NIR exposure, allowing concurrent detection and removal of targets.
The aggregation leads to efficient removal or clearance of targets via biological systems such as liver and spleen.
Documented Applications
Controlling the pharmacokinetics and clearance of drugs in vivo by conjugation to IR700 and subsequent NIR-induced removal.
Removing undesired agents including toxins, pathogens, spores, metals, and unwanted cells from environmental or food samples.
Isolating or separating target molecules such as proteins, nucleic acids, cells, peptides, lectins, carbohydrates, and small molecules in laboratory and clinical settings.
Selective killing and removal of targeted cells within mixed cell populations in vitro, ex vivo and in vivo (e.g., tumors and cell cultures).
Using wearable devices incorporating NIR LEDs or lasers to expose subjects to NIR light and achieve continuous photo-controlled removal of circulating targets.
Removing pathogens including bacteria, fungi, viruses, and spores from subjects by IR700 conjugates specific to pathogens followed by NIR irradiation.
Isolation or removal of therapeutic, recreational, or toxic drugs from subjects to modulate drug activity or treat overdose.
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