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-11781955-B2
Publication Date
2023-10-10
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
The invention provides IR700-molecule conjugates and methods for their use to remove or isolate a target from a sample in vitro or in vivo. The core innovation centers on the observation that exposure of IR700 to near infrared (NIR) light cleaves a portion of the IR700, changing it from a hydrophilic to a hydrophobic molecule, resulting in aggregation of the IR700 and anything bound to it. This photo-controlled change enables controlled removal of target agents from various environments including solutions, cells or organisms.
The disclosed IR700-molecule conjugates enable photo-controlled manipulation of pharmacokinetics of drugs in vivo, removal of undesired agents from environmental or food samples, and isolation of target molecules in laboratory settings. Upon exposure to NIR light, the phthalocyanine IRDye700DX (IR700) conjugated to specific binding agents binds targets, and subsequent illumination causes cleavage leading to hydrophobic reactive species that aggregate, facilitating separation or elimination of the target complex.
The problem solved by this invention is the difficulty in isolating and eliminating a selected biomolecule or cell among mixtures of biomolecules or cells in complex environments such as solutions, cells, and whole organisms. Current technologies lack efficient means for selective, photo-controlled removal or isolation of target molecules or cells, especially in vivo. The methods described offer a novel approach enabling precise control of target removal via IR700 conjugates and NIR irradiation.
Claims Coverage
The patent includes two independent claims that address methods for removing targets from samples and subjects using IR700-molecule conjugates and NIR irradiation.
Photo-controlled aggregation and removal of target from a sample
A method that involves contacting a sample with an IR700 conjugated molecule comprising a specific binding agent to form a complex with a target, followed by irradiation at 660-710 nm at a sufficient dose to cleave hydrophilic side chains of IR700 converting the complex to hydrophobic form which aggregates, permitting separation and removal of the target from the sample.
In vivo removal and detection of target from a subject
A method comprising systemic administration of an IR700 conjugated molecule containing a specific binding agent to a subject, allowing binding to the target, irradiating the subject with NIR to cleave and hydrophobize the complex, permitting aggregation in the subject, followed by obtaining a urine or bowel movement sample containing the aggregate and detecting the removed target from the subject.
The inventive features focus on using IR700 conjugates that change hydrophilicity upon NIR irradiation to cause aggregation and facilitate selective removal of targets from samples or subjects, including subsequent detection of removed targets in vivo.
Stated Advantages
Provides photo-controlled ways to control pharmacokinetics of drugs in vivo.
Enables efficient removal or isolation of target molecules, cells, or agents from complex biological, environmental, or food samples.
Allows selective elimination of specific cell populations without damaging neighboring cells or tissue.
Facilitates improved purification processes by removing unwanted impurities, toxins, or pathogens from samples.
Documented Applications
Controlling pharmacokinetics and removal of drugs and pharmaceutical agents in vivo.
Removal of toxins, pathogens, metals, spores, and drugs from environmental and food samples.
Isolating, separating, or eliminating target proteins, nucleic acids, or cells from laboratory or clinical samples in vitro, ex vivo, or in vivo.
Selective killing and elimination of specific cell populations in mixed cell cultures, 3D spheroids, and in vivo tumors for regenerative medicine and cancer therapy.
Use with wearable NIR LED devices to treat subjects privately and continuously by activating IR700-conjugated targets in superficial vessels.
Removal of undesirable immune cells to modulate immune response in autoimmune diseases, cancer, or allergies.
Use in combination with apheresis or isolated organ perfusion to remove targets from blood or organs.
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