Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe

Ryan, Lucas S.; Gerberich, Jeni; Cao, Jian; An, Weiwei; Jenkins, Becky A.; Mason, Ralph P.; Lippert, Alexander R.

doi:10.1021/acssensors.9b00360

Cited by 45 publications

(37 citation statements)

References 46 publications

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“…Such a generic molecular design enables ultrasensitive chemiluminescence imaging of various enzymes (e.g. nitroreductase, [15] γ‐glutamyl transpeptidase, [16] cathepsins, [17] etc [18, 19] …”

Section: Figurementioning

confidence: 99%

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

et al. 2020

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Chemiluminescence imaging is imperative for diagnostics and imaging due to its intrinsically high sensitivity. To improve in vivo detection of biomarkers, chemiluminophores that simultaneously possess near‐infrared (NIR) emission and modular structures amenable to construction of activatable probes are highly desired; however, these are rare. Herein, we report two chemiluminophores with record long NIR emission (>750 nm) via integration of dicyanomethylene‐4H‐benzothiopyran or dicyanomethylene‐4H‐benzoselenopyran with dioxetane unit. Caging of the chemiluminophores with different cleavable moieties produces NIR chemiluminescence probes (NCPs) that only produce signals upon reaction with reactive oxygen species or enzymes, for example, β‐galactosidase, with a tissue‐penetration depth of up to 2 cm. Thus, this study provides NIR chemiluminescence molecular scaffolds applicable for in vivo turn‐on imaging of versatile biomarkers in deep tissues.

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Section: Figurementioning

confidence: 99%

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

et al. 2020

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“…Enzymes (cathepsins, [ 28 ] γ‐glutamyl transpeptidase, [ 29 ] nitroreductase, [ 30 ] etc. ), as common biomarkers, have contributed novel insights into designing and developing activatable CL probes based on Schaap's dioxetane.…”

Section: Nir Chemiluminescence Imagingmentioning

confidence: 99%

Organic Semiconducting Luminophores for Near‐Infrared Afterglow, Chemiluminescence, and Bioluminescence Imaging

Yin

Liew

et al. 2021

Adv Funct Materials

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Optical imaging has played a pivotal role in deciphering in vivo bioinformatics but is limited by shallow penetration depth and poor imaging performance owing to interfering tissue autofluorescence induced by concurrent photoexcitation. The emergence of near‐infrared (NIR) self‐luminescence imaging independent of real‐time irradiation has timely addressed these problems. There are two main kinds of self‐luminescent agents, namely inorganic and organic luminophores. Inorganic luminophores usually suffer from long‐term biotoxicity concerns resulting from potential heavy‐metal ions leakage and nonbiodegradability, which hinders their further translational application. In contrast, organic luminophores, especially organic semiconducting luminophores (OSLs) with good biodegradable potential, tunable design, and outstanding optical properties, are preferred in biological applications. This review summarizes the recent progress of OSLs used in NIR afterglow, chemiluminescence, and bioluminescence imaging. Molecular manipulation and nanoengineering approaches of OSLs are discussed, with emphasis on strategies that can extend the emission wavelength from visible to NIR range and amplify luminescence signals. This review concludes with a discussion of current challenges and possible solutions of OSLs in the self‐luminescence field.

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“…However, these probes were only administrated through intratumoral injection, which has limited application in the clinical settings for deep orthotopic tumor hypoxia tracking. [143,144] Alternatively, developing hypoxia-specific fluorescence reporter genes is a promising strategy that allows for accurate tracking of the hypoxia-responsive transcriptional activity in vivo, and does not require external probes. The Bhujwalla group developed an HRE-driven imaging strategy that utilizes two optical reporters with different half-lives to detect temporal changes in hypoxia and HIF activity.…”

Section: Other Imaging Strategiesmentioning

confidence: 99%

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

Cheng

Zheng

2020

Adv Healthcare Materials

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Hypoxia is a ubiquitous feature of solid tumors, which plays a key role in tumor angiogenesis and resistance development. Conventional hypoxia detection methods lack continuous functional detection and are generally less suitable for dynamic hypoxia measurement. Optical sensors hereby provide a unique opportunity to noninvasively image hypoxia with high spatiotemporal resolution and enable real‐time detection. Therefore, these approaches can provide a valuable tool for personalized treatment planning against this hallmark of aggressive cancers. Many small optical molecular probes can enable analyte triggered response and their photophysical properties can also be fine‐tuned through structural modification. On the other hand, optical nanoprobes can acquire unique intrinsic optical properties through nanoconfinement as well as enable simultaneous multimodal imaging and drug delivery. Furthermore, nanoprobes provide biological advantages such as improving bioavailability and systemic delivery of the sensor to enhance bioavailability. This review provides a comprehensive overview of the physical, chemical, and biological analytes for cancer hypoxia detection and focuses on discussing the latest nano‐ and molecular developments in various optical imaging approaches (fluorescence, phosphorescence, and photoacoustic) in vivo. Finally, this review concludes with a perspective toward the potentials of these optical imaging approaches in hypoxia detection and the challenges with molecular and nanotechnology design strategies.

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Kinetics-Based Measurement of Hypoxia in Living Cells and Animals Using an Acetoxymethyl Ester Chemiluminescent Probe

Cited by 45 publications

References 46 publications

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

Organic Semiconducting Luminophores for Near‐Infrared Afterglow, Chemiluminescence, and Bioluminescence Imaging

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

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