Abstract: Embodiments of the synthesis, radiolabeling and biological applications of an activatable tracer that undergoes intramolecular cyclization and aggregation upon activation by cleavage of a blocking moiety are provided. The probes of the disclosure allow for target-controlled self-assembly of small molecules in living subjects for imaging and drug delivery. The aggregated nanoprobes of the disclosure may be detectable optically, by PET detection, magnetic resonance imaging, and the like depending on the detectable reporter attached to the nanoprobe.

Abstract: Embodiments of the synthesis, radiolabeling and biological applications of an activatable tracer that undergoes intramolecular cyclization and aggregation upon activation by cleavage of a blocking moiety are provided. The probes of the disclosure allow for target-controlled self-assembly of small molecules in living subjects for imaging and drug delivery. The aggregated nanoprobes of the disclosure may be detectable optically, by PET detection, magnetic resonance imaging, and the like depending on the detectable reporter attached to the nanoprobe.

Abstract: Provided is a mitochondrial copper depleting strategy that exploits the potential vulnerability for this metabolic by cancer cells such as Triple Negative Breast Cancer cells. A nanoparticle is provided that comprises a self-reporting copper-depleting moiety (CDM) embedded in or on the matrix comprising a semi-conducting polymer and a phospholipid-polyethylene glycol (PEG). The positively charged copper-depleting complex targets mitochondria and deprives cytochrome c oxidase of its necessary copper co-factor. Inhibition of the electron transport chain complex IV compromises oxygen consumption and abrogates fatty acid oxidation, resulting in energy deficiency induced apoptosis of the targeted cancer cells. The copper-depleting nanoparticle can report the copper depleting status through multimodal optical signal changes while decreasing the copper level in tumors to inhibit tumor growth with low toxicity and significantly prolonged survival.

Abstract: Embodiments of the synthesis, radiolabeling and biological applications of an activatable tracer that undergoes intramolecular cyclization and aggregation upon activation by cleavage of a blocking moiety are provided. The probes of the disclosure allow for target-controlled self-assembly of small molecules in living subjects for imaging and drug delivery. The aggregated nanoprobes of the disclosure may be detectable optically, by PET detection, magnetic resonance imaging, and the like depending on the detectable reporter attached to the nanoprobe.

Abstract: The present invention discloses a probe useful for the selective detection of metallo-beta-lactamases, in particular carbapenemases, thereby distinguishing those species of bacteria that are carbapenem-resistant from bacterial strains that are sensitive. Cephalospori based probes that have the 6,7 R,R configuration are susceptible to cleavage by beta-lactamases but cannot distinguish between cleavage by metallo-beta-lactamases and other beta-lactamases. By modifying a side group of the cephalosporin, selectivity can be introduced allowing the probes to distinguish between various types of metallo-beta-lactamases.

Abstract: The compositions of the present disclosure provide novel fluorogenic probes for use in the specific imaging and detection of mycobacteria species, and in particular ?-lactam-antibiotic resistant. Specificity for mycobacteria is conferred on these probes by incorporating a moiety that specifically targets the unique trapping mechanism of the DprE1 found in in mycobacteria. Accordingly, only Mycobacteria species that express both a ?-lactamase and DprE1 enable both the activation of the caged fluorescent probe, and the affixing of the released fluorescent probes to the bacteria cells through the functioning reduction-covalent binding mechanism. Advantageously, such a probe is able, at its most sensitive, to allow single mycobacterium detection.

Abstract: ?-Lactamase substrates and methods for using the substrates to detect ?-lactamase and to diagnose tuberculosis.

Abstract: The present inventors have harnessed the targeting of nanoparticles to tumor sites, combined with the tumor site specific elevated MMP-14 activity within one conjugate to simultaneously deliver a vascular disrupting agent (VDA) and a MRI contrast agent to a tumor site. The MMP activatable conjugate of the present invention provides both therapeutic and diagnostic functions—and is referred to as a “theranostic”. The theranostic conjugate of the present invention achieves the benefits of tumor site specificity, VDA delivery and MRI contrast agent delivery in a single theranostic conjugate. Consequently, the present invention provides a cancer “theranostic” which improves therapeutic efficacy while simultaneously reducing dose-limiting systemic toxicities and provides a tool for rapidly and non-invasively identifying tumor location, monitoring drug delivery and pharmacodynamics.

Abstract: Provided are embodiments of a small molecule tracer for positron emission tomography (PET) imaging of the enzyme activity of PARP-1 that is responsible for DNA-damage sensing and critically involved in radiation therapy and some chemotherapy response mechanisms. These PARP-1 tracers are derivatives of nicotinamide adenine dinucleotide (NAD), which is the natural substrate for PARP-1. Provided are NAD derivatives that include a linker moiety to which may be attached a label moiety such as a PET detectable fluorine to generate a 6N-(triazo-PEG2-18F)-NAD. Especially advantageous for use in PET and MRI scanning detection systems is the attachment of a chelating agent that allows for the formation of a chelator-metal ion complex.

Abstract: ?-Lactamase substrates and methods for using the substrates to detect ?-lactamase and to diagnose tuberculosis.

Abstract: Encompassed are embodiments of activatable nanoprobes useful for in vivo longitudinal imaging of drug hepatotoxicity with oxidative and nitrosative stress as the safety biomarkers. Both H2O2 and ONOO? are important mediators of radical stress. Two channels of optical detection, intrinsically free from cross-talk, were engineered into superconducting polymer nanoparticles to generate chemiluminescence resonance energy transfer between the conjugated polymer matrix of the nanoparticle and an incorporated chemiluminescent substrate allowing for the luminescent detection of H2O2 and fluorescence resonance energy transfer between the polymer matrix and an oxidation-degradable fluorophore for ratiometric detection of ONOO These nanoprobes have been applied for real-time in vivo monitoring of hepatotoxicity resulting from challenges from drugs.

Abstract: ?-Lactamase substrates and methods for using the substrates to detect ?-lactamase and to diagnose tuberculosis.

Abstract: ?-Lactamase substrates and methods for using the substrates to detect ?-lactamase diagnose tuberculosis.

Abstract: For whole animal in-situ and real-time imaging of inflammation, a dual-color fluorescent nanoprobe is provided for the detection of reactive oxygen and nitrogen species (RONS) in inflammatory microenvironments. The nanoprobes of the disclosure are a RONS-responsive energy transferring nanosystem of a fluorescent conjugated polymer core and a PEG-shell linked with RONS-sensing antennae as a FRET acceptor. These nanoprobes allow in vivo imaging of the entire process of inflammation from the release of local tissue distress signals, to the action of leukocytes and macrophages late in the process of inflammation, through to restitution, allowing in whole-body diagnosis and monitoring of inflammatory diseases.

Abstract: Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

Abstract: The compositions of the present disclosure provide novel fluorogenic probes for use in the specific imaging and detection of mycobacteria species, and in particular ?-lactam-antibiotic resistant. Specificity for mycobacteria is conferred on these probes by incorporating a moiety that specifically targets the unique trapping mechanism of the DprE1 found in in mycobacteria. Accordingly, only Mycobacteria species that express both a ?-lactamase and DprE1 enable both the activation of the caged fluorescent probe, and the affixing of the released fluorescent probes to the bacteria cells through the functioning reduction-covalent binding mechanism. Advantageously, such a probe is able, at its most sensitive, to allow single mycobacterium detection.

Abstract: Provided herein provided is an assay system for monitoring drug susceptibility of a pathogenic bacteria comprising color-producing substrates for a beta-lactamase of the pathogenic bacteria, an assay device for visibly detecting a product of the beta-lactamase on the substrate thereof and a reader configured to quantify the visibly detected product. Also provided is an in vitro method to determine susceptibility to a drug effective against a pathogenic bacteria, for example, a pathogenic Mycobacteria, that has a beta-lactamase activity. An excitation wavelength is delivered to a biological sample obtained from a subject having an infection from the pathogenic bacteria in the presence of a beta-lactamase substrate. The intensity of a signal, such as a fluorescent, luminescent or colorimetric signal, at an emission wavelength of a product of the beta-lactamase on the subject is correlated to drug susceptibility.

Abstract: The present invention discloses a probe useful for the selective detection of metallo-beta-lactamases, in particular carbapenemases, thereby distinguishing those species of bacteria that are carbapenem-resistant from bacterial strains that are sensitive. Cephalospori based probes that have the 6,7 R,R configuration are susceptible to cleavage by beta-lactamases but cannot distinguish between cleavage by metallo-beta-lactamases and other beta-lactamases.

Abstract: The present inventors have harnessed the targeting of nanoparticles to tumour sites, combined with the tumour site specific elevated MMP-14 activity within one conjugate to simultaneously deliver a vascular disrupting agent (VDA) and a MRI contrast agent to a tumour site. The MMP activatable conjugate of the present invention provides both therapeutic and diagnostic functions—and is referred to as a “theranostic”. The theranostic conjugate of the present invention achieves the benefits of tumour site specificity, VDA delivery and MRI contrast agent delivery in a single theranostic conjugate. Consequently, the present invention provides a cancer “theranostic” which improves therapeutic efficacy whilst simultaneously reducing dose-limiting systemic toxicities and provides a tool for rapidly and non-invasively identifying tumour location, monitoring drug delivery and pharmacodynamics.

Abstract: Provided herein are assays and in vitro methods to determine susceptibility to a drug effective against a pathogenic bacteria, for example, a pathogenic Mycobacteria, that has a beta-lactamase activity. An excitation wavelength is delivered to a biological sample obtained from a subject having an infection from the pathogenic bacteria in the presence of a beta-lactamase substrate. The intensity of a signal, such as a fluorescent, luminescent or colorimetric signal, at an emission wavelength of a product of the beta-lactamase on the subject is correlated to drug susceptibility. Also provided is an assay system for monitoring drug susceptibility of a pathogenic bacteria comprising color-producing substrates for a beta-lactamase of the pathogenic bacteria, an assay device for visibly detecting a product of the beta-lactamase on the substrate thereof and a reader configured to quantify the visibly detected product.