New directions of activity-based sensing forin vivoNIR imaging

East, Amanda; Lucero, Melissa Y.; Chan, Jefferson

doi:10.1039/d0sc03096a

“…Unlike fluorescence, photoacoustic, or chemiluminescence imaging, the generation of a bioluminescent readout requires the presence of luciferase. 34,70 In a typical BL imaging experiment, a higher signal indicates there are more cells, and this is commonly used to track tumor progression. However, in the case of analyte sensing, the dependence on luciferase activity can confound results.…”

Section: Resultsmentioning

confidence: 99%

“…32 Unlike fluorescence imaging (light-in, light-out) and photoacoustic imaging (light-in, sound-out), bioluminescence (BL) imaging does not rely on external light excitation to generate a readout. 33,34 As such, BL imaging offers improved sensitivity by circumventing incident light, as well as decreased background that results from autofluorescence or endogenous chromophores that are photoacoustic-active. 35 Although numerous ABS probes for BL imaging have been developed, [36][37][38][39][40][41][42][43][44][45][46][47] deep tissue imaging of NO in the TME has remained elusive.…”

Section: Introductionmentioning

confidence: 99%

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

Yadav¹,

Lee²,

Lucero³

et al. 2021

Preprint

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Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due to its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities of NO in response to the nascent tumor. However, it is believed that this fades over time and reaches a concentration that supports the tumor microenvironment (TME). These complex dynamics are further complicated by other factors, such as diet and oxygenation, making it challenging to establish a complete picture of NO’s impact on tumor progression. Although many activity-based sensing (ABS) probes for NO have been developed, only a small fraction have been employed in vivo and fewer yet are practical in cancer models where the NO concentration is < 200 nM. To overcome this outstanding challenge, we have developed BL660-NO, the first ABS probe for NIR bioluminescence imaging of NO in cancer. Owing to the low intrinsic background, high sensitivity, and deep tissue imaging capabilities of our design, BL660-NO was successfully employed to visualize endogenous NO in cellular systems, a human liver metastasis model, and a murine breast cancer model. Importantly, its exceptional performance facilitated the design of a dietary study to examine the impact of NO on the TME by varying the intake of fat. BL660-NO provides the first direct molecular evidence that intratumoral NO becomes elevated in mice fed a high-fat diet who became obese with larger tumors compared to control animals on a low-fat diet. These results indicate that an inflammatory diet can increase NO production via recruitment of macrophages and overexpression of iNOS which in turn can drive tumor progression.

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“…Unlike fluorescence, photoacoustic, or chemiluminescence imaging, the generation of a bioluminescent readout requires the presence of luciferase. 34,70 In a typical BL imaging experiment, a higher signal indicates there are more cells, and this is commonly used to track tumor progression. However, in the case of analyte sensing, the dependence on luciferase activity can confound results.…”

Section: Discussionmentioning

confidence: 99%

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

Ak¹,

Mc²,

Lucero³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Nitric oxide (NO) plays a critical role in acute and chronic inflammation. NO’s contributions to cancer are of particular interest due to its context-dependent bioactivities. For example, immune cells initially produce cytotoxic quantities of NO in response to the nascent tumor. However, it is believed that this fades over time and reaches a concentration that supports the tumor microenvironment (TME). These complex dynamics are further complicated by other factors, such as diet and oxygenation, making it challenging to establish a complete picture of NO’s impact on tumor progression. Although many activity-based sensing (ABS) probes for NO have been developed, only a small fraction have been employed in vivo and fewer yet are practical in cancer models where the NO concentration is < 200 nM. To overcome this outstanding challenge, we have developed BL660-NO, the first ABS probe for NIR bioluminescence imaging of NO in cancer. Owing to the low intrinsic background, high sensitivity, and deep tissue imaging capabilities of our design, BL660-NO was successfully employed to visualize endogenous NO in cellular systems, a human liver metastasis model, and a murine breast cancer model. Importantly, its exceptional performance facilitated the design of a dietary study to examine the impact of NO on the TME by varying the intake of fat. BL660-NO provides the first direct molecular evidence that intratumoral NO becomes elevated in mice fed a high-fat diet who became obese with larger tumors compared to control animals on a low-fat diet. These results indicate that an inflammatory diet can increase NO production via recruitment of macrophages and overexpression of iNOS which in turn can drive tumor progression.

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“…[1][2][3][4][5][6] One ambitious goal of uorescence sensing is non-invasive monitoring and detection of physiological parameters or clinically relevant species. 7,8 It has been already possible to measure uorescence signals through the skin, and the measurement results can accurately reect the concentration of the analytes. 9 To achieve uorescence bio-detection at deeper tissue penetration depths for detecting or monitoring physiological parameters and processes in the body, interaction between photons (excitation and emission) and bio-tissues has been investigated.…”

Section: Introductionmentioning

confidence: 99%

Activatable fluorescence sensors forin vivobio-detection in the second near-infrared window

Zhao

¹

,

Li

²

,

Zhang

³

et al. 2021

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New directions of activity-based sensing forin vivoNIR imaging

Abstract:
In vivo imaging is a powerful approach to study biological processes. Beyond cellular methods, in vivo studies allow for biological stimuli (small molecules or proteins) to be studied in their...

Cited by 79 publications

References 123 publications

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

Activatable fluorescence sensors forin vivobio-detection in the second near-infrared window

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New directions of activity-based sensing forin vivoNIR imaging

Abstract: In vivo imaging is a powerful approach to study biological processes. Beyond cellular methods, in vivo studies allow for biological stimuli (small molecules or proteins) to be studied in their...

Cited by 79 publications

References 123 publications

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

NIR Bioluminescence Probe Enables Discovery of Diet-Induced Modulation of the Tumor Microenvironment via Nitric Oxide

Activatable fluorescence sensors forin vivobio-detection in the second near-infrared window

Contact Info

Product

Resources

About

Abstract:
In vivo imaging is a powerful approach to study biological processes. Beyond cellular methods, in vivo studies allow for biological stimuli (small molecules or proteins) to be studied in their...