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Publication Number
US-10124072-B2
Publication Date
2018-11-13
Expiration Date
Abstract
The disclosure features methods that include: administering to a subject a composition that includes particles, where each one of the particles features at least one targeting group that binds to a structural entity in the subject and at least one reacting group that reacts chemically with a reactive oxygen species in the subject, and where the particle emits luminescence when the reaction occurs; detecting the luminescence emission from the particles; and displaying an image of the subject showing locations of at least some reactive oxygen species in the subject based on the detected luminescence.
Core Innovation
The invention provides a method for in-vivo imaging of reactive oxygen species in a subject. The method administers a composition comprising particles that include a core with at least one reacting group that chemically reacts with a reactive oxygen species and emits radiation at a first wavelength, and at least one luminescent group comprising at least one lanthanide element that absorbs a portion of the radiation at the first wavelength and emits luminescence at a second wavelength different from the first wavelength.
Each particle includes a first coating formed of a first polysaccharide material surrounding the core, and a second coating formed of a second polysaccharide material surrounding the first coating. The second coating comprises at least one targeting group that binds to a structural entity in the subject, and detecting the luminescence emission from the particles supports displaying an image of the subject showing locations of at least some reactive oxygen species based on the detected luminescence.
Claims Coverage
The document contains one independent claim directed to a method that administers lanthanide-luminescent, ROS-reactive particles with dual polysaccharide coatings and targeting groups, followed by detecting luminescence and displaying an image showing locations of reactive oxygen species. Dependent claim refinements add wavelength-based detection features, identify specific targeting groups and reactive oxygen species, and introduce particle subsets for multiplexing.
Lanthanide luminescent ROS-reactive imaging particles with wavelength conversion
Particles have a core with at least one reacting group that chemically reacts with a reactive oxygen species and emits radiation at a first wavelength, and at least one lanthanide luminescent group that absorbs a portion of the radiation at the first wavelength and emits luminescence at a second wavelength different from the first wavelength.
Dual polysaccharide coatings with structural entity targeting
A first coating formed of a first polysaccharide material surrounds the core, and a second coating formed of a second polysaccharide material surrounds the first coating, wherein the second coating comprises at least one targeting group that binds to a structural entity in the subject.
Luminescence detection and image display of ROS locations
The method detects the luminescence emission from the particles and displays an image of the subject showing locations of at least some reactive oxygen species based on the detected luminescence.
Imaging using unfiltered emitted radiation and wavelength thresholds
In embodiments, the imaging is based on unfiltered emitted radiation that includes luminescence emission, and luminescence emission is detected at a wavelength of 500 nm or more.
Antibody targeting for structural entity binding
In embodiments, the at least one targeting group includes at least one antibody.
Specific reactive oxygen species selection for imaging
In embodiments, the reactive oxygen species includes singlet oxygen.
Multiplexing with particle subsets using different targeting and reacting groups
In embodiments, particles are arranged into a first subset and a second subset, where the first subset has a first targeting group and a first reacting group and the second subset has a second targeting group and a second reacting group, with the first and second targeting groups being different.
Overall, the claims cover an imaging method that uses ROS-reactive cores coupled to lanthanide luminescent groups for wavelength-shift emission, encapsulated by dual polysaccharide coatings and a targeting group that binds to a structural entity. The method relies on detecting luminescence emission and displaying an image indicating ROS locations, with dependent features covering unfiltered emitted radiation and wavelength thresholds, antibody targeting, specific ROS types such as singlet oxygen, and multiplexing via particle subsets with differing targeting and reacting configurations.
Stated Advantages
Displays an image showing locations of at least some reactive oxygen species in the subject based on detected luminescence emission.
Enables imaging with luminescence emission at a second wavelength different from the first wavelength using lanthanide elements.
Supports targeting of the particles to structural entities in the subject using targeting groups including antibodies.
Supports multiplexing using particle subsets having different targeting groups and different reacting groups.
Documented Applications
In-vivo imaging of reactive oxygen species in living subjects.
Localization of reactive oxygen species in lung and liver tissue in mouse studies using LPS-induced inflammation.
Imaging embodiments include multiplexing reactive oxygen species localization using particle subsets with different targeting groups and luminescent features.
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