In vivo imaging of enzymatic activity
Inventors
Ansaldi, Daniel • Francis, Kevin P. • Singh, Rajendra • Zhang, Ning
Assignees
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Publication Number
US-9446151-B2
Publication Date
2016-09-20
Expiration Date
Abstract
Compositions and methods are described for detecting enzyme activity in a live organism (e.g., animal) are provided.
Core Innovation
The invention describes nanoparticle absorbed chemiluminescence (NAC) for in vivo imaging of endogenous enzymatic activity linked to oxidative stress. A chemiluminescent enzymatic probe generates short-wavelength chemiluminescence in the presence of a product of endogenous enzyme activity in a live animal, and an unconjugated near-infrared (NIR) nanoparticle absorbs the chemiluminescence to provide a red-shifted signal for detection.
The described approach uses an endogenous enzymatic activity cascade associated with oxidative stress to produce enzyme products that drive chemiluminescence from a luminol or luminol derivative type probe. The method relates to oxidative stress associated species and enzymatic components including ROS, myeloperoxidase (MPO), and hypochlorous acid (HOCl). The NIR nanoparticle emits light upon exposure to the chemiluminescence emitted by the probe.
The document further describes use of NIR nanoparticles such as quantum dots, including QD800, that absorb and red-shift the chemiluminescence, optionally with targeting moieties. Imaging is performed in vivo to detect endogenous activity with improved sensitivity relative to probe-only detection, and the content additionally references formulation evaluation and use of NIR filters and imaging systems for signal detection.
Claims Coverage
The partial content identifies one independent claim. It covers an injectable composition combining a chemiluminescent enzymatic probe with an unconjugated NIR nanoparticle to generate light in a live animal via a two-stage sequence involving endogenous enzyme activity and nanoparticle exposure to chemiluminescence. The independent claim’s inventive coverage is centered on NAC where the NIR nanoparticle emits light upon exposure to probe-emitted chemiluminescence.
Injectable composition with chemiluminescent enzymatic probe and unconjugated NIR nanoparticle
An injectable composition consisting of a chemiluminescent enzymatic probe and an unconjugated near-infrared (NIR) nanoparticle, wherein the composition is injected into a live animal such that the chemiluminescent enzymatic probe emits chemiluminescence in the presence of a product of endogenous enzyme activity in the live animal.
Two-stage light generation in live animals via exposure of NIR nanoparticle to probe chemiluminescence
The composition is configured such that the NIR particle emits light upon exposure to the chemiluminescence emitted from the chemiluminescent probe.
Across the identified independent claim, the main inventive concept is NAC in an injectable format: endogenous enzyme activity drives chemiluminescence from a chemiluminescent enzymatic probe, and an unconjugated NIR nanoparticle emits light upon exposure to that chemiluminescence for in vivo detection.
Stated Advantages
Enhanced detection sensitivity compared with luminol alone.
Reduced need for exogenous enzymes or excitation light.
Red-shift to near-infrared wavelengths to improve detection of emitted signal.
Documented Applications
In vivo imaging of endogenous enzymatic activity linked to oxidative stress, including imaging associated with LPS-induced lung inflammation and detection of tumor metastases in lung, knee, and cranial regions.
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