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Publication Number
US-11040118-B2
Publication Date
2021-06-22
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 enables in-vivo imaging of reactive oxygen species in a subject by administering targeted, ROS-reacting luminescent particles and detecting emitted luminescence to generate images and localization/quantification of reactive oxygen species. Each particle includes a core with at least one reacting group that reacts chemically with a reactive oxygen species and at least one luminescent agent comprising at least one lanthanide element that emits luminescence in response to the reaction of the reacting group.
The particles further include a first coating material encapsulating the core and a second coating material encapsulating the first coating material. The second coating material comprises at least one targeting group that binds to a structural entity in the subject, enabling targeted imaging.
The document also describes multiplexing by using particle subsets, with different targeting groups and corresponding reacting and luminescent characteristics. In one described approach, particle subsets are associated with distinct lanthanide emission wavelengths above 500 nm to support selective detection.
Claims Coverage
The partial content includes two independent claims covering a targeted ROS-reacting luminescent particle composition and a kit for imaging reactive oxygen species in a living subject. Each independent claim requires a two-coating particle architecture with a targeting group on the second coating and a reacting-lanthanide luminescence core.
Targeted ROS-reacting lanthanide luminescent particle composition
A suspension medium and a plurality of particles in which each particle comprises a core with at least one reacting group that reacts chemically with a reactive oxygen species in a subject and at least one luminescent agent comprising at least one lanthanide element that emits luminescence in response to the reaction of the reacting group; a first coating material encapsulating the core; and a second coating material encapsulating the first coating material and comprising at least one targeting group that binds to a structural entity in the subject.
Kit for imaging reactive oxygen species in a living subject
A housing containing a suspension medium and a plurality of particles, where each particle comprises a core with at least one reacting group that reacts chemically with a reactive oxygen species in the living subject and at least one luminescent agent comprising at least one lanthanide element that emits luminescence in response to the reaction of the reacting group; a first coating material encapsulating the core; and a second coating material encapsulating the first coating material and comprising at least one targeting group that binds to a structural entity in the living subject.
Across both independent claims, the core inventive structure is a particle whose ROS-reacting core drives lanthanide-based luminescence, encapsulated by a first coating and further encapsulated by a second coating carrying a targeting group that binds a structural entity in the subject, with the second independent claim additionally requiring a kit format with a housing.
Stated Advantages
Enables in-vivo imaging of reactive oxygen species by detecting emitted luminescence to generate images and localization/quantification.
Targeted imaging enabled by a second coating material comprising at least one targeting group that binds to a structural entity in the subject.
Selective detection and multiplexing based on distinct lanthanide emission characteristics and emission wavelengths above 500 nm.
Reduction of autofluorescence background is described in the context of imaging selectivity.
Avoids donor/acceptor bead FRET proximity constraints is described as part of the preparation rationale.
Documented Applications
Imaging reactive oxygen species in a living subject.
Detecting reactive oxygen species species including singlet oxygen, hydroxyl radical, hypochlorous acid, superoxide radical, nitric oxide, and hydrogen peroxide (as explicitly enumerated as reactive oxygen species).
In vivo imaging in murine subjects with LPS-induced inflammation using antibody-conjugated particles (e.g., Ly6G for lung targeting) is described in the partial content.
Multiplexed detection using particle subsets with different targeting groups and/or distinct lanthanide emission wavelengths above 500 nm is described.
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