In vivo photoacoustic potassium imaging of the tumor microenvironment

Tan, Joel W. Y.; Folz, Jeff; Kopelman, Raoul; Wang, Xueding

doi:10.1364/boe.393370

Cited by 15 publications

(15 citation statements)

References 34 publications

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“…The distributions of other ENSCs (or their uptake) have also been partially revealed in vivo or in vitro to varying degrees, such as glutamine, amino acids, and metal ions ( 165 , 174 – 177 ). The distributions of some of these molecules are correlated with the function of immune cells.…”

Section: Spatially-based Extracellular Nonspecific Chemical (Ensc) Gradients Orchestrate Immune Cell Functionmentioning

confidence: 99%

“…The distributions of some of these molecules are correlated with the function of immune cells. For instance, the altered gradient of Na + is correlated with the polarization of macrophages, probably in a tissue-specific manner ( 176 ), and increased K + levels in tumors can suppress effector T cell function and prevent immune cells from maturing ( 177 ). However, researchers still do not comprehensively understand the significance of their effects on immune cells in a complex real TME, which must be further established.…”

Section: Spatially-based Extracellular Nonspecific Chemical (Ensc) Gradients Orchestrate Immune Cell Functionmentioning

confidence: 99%

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Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

et al. 2021

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Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.

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Section: Spatially-based Extracellular Nonspecific Chemical (Ensc) Gradients Orchestrate Immune Cell Functionmentioning

confidence: 99%

Section: Spatially-based Extracellular Nonspecific Chemical (Ensc) Gradients Orchestrate Immune Cell Functionmentioning

confidence: 99%

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

et al. 2021

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“…Finally, targeted potassium probes were developed using ionophore-based solvatochromic dye-based K+-sensing nanoparticle (SDKNP). 257 The probes were tested on tumor-bearing mice and showed remarkable PA signal difference due to the higher concentration of

in tumors. Further, the group noticed slightly higher concentrations of

inside the tumor’s core as opposed to the tumor’s periphery.…”

Section: Molecular Photoacoustic Imagingmentioning

confidence: 99%

Looking deep inside tissue with photoacoustic molecular probes: a review

2022

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. Significance: Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic imaging (PAI) can overcome some of the challenges of pure optical or ultrasound imaging to provide high-resolution deep tissue imaging. However, label-free PAI signals from light absorbing chromophores within the tissue are nonspecific. The use of exogeneous contrast agents (probes) not only enhances the imaging contrast (and imaging depth) but also increases the specificity of PAI by binding only to targeted molecules and often providing signals distinct from the background. Aim: We aim to review the current development and future progression of photoacoustic molecular probes/contrast agents. Approach: First, PAI and the need for using contrast agents are briefly introduced. Then, the recent development of contrast agents in terms of materials used to construct them is discussed. Then, various probes are discussed based on targeting mechanisms, in vivo molecular imaging applications, multimodal uses, and use in theranostic applications. Results: Material combinations are being used to develop highly specific contrast agents. In addition to passive accumulation, probes utilizing activation mechanisms show promise for greater controllability. Several probes also enable concurrent multimodal use with fluorescence, ultrasound, Raman, magnetic resonance imaging, and computed tomography. Finally, targeted probes are also shown to aid localized and molecularly specific photo-induced therapy. Conclusions: The development of contrast agents provides a promising prospect for increased contrast, higher imaging depth, and molecularly specific information. Of note are agents that allow for controlled activation, explore other optical windows, and enable multimodal use to overcome some of the shortcomings of label-free PAI.

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“…1,2 Measurements of metal ions, especially K + , in the tumor interstitial fluid are useful for understanding and management of cancer resistance to immunotherapy. 3,4 Monitoring of ion fluxes across membranes of cells or bacteria is a valuable method to study cellular/bacterial physiology and screen ion channel-targeted drugs. 5,6 Droplet microfluidics that can be integrated with ion-sensing chemistries may become an enabling platform for these applications.…”

mentioning

confidence: 99%

“…The concentration of electrolytes in bodily fluids such as blood, plasma, sweat, saliva, and tear is of major importance for the assessment of the health state of an individual. , Measurements of metal ions, especially K + , in the tumor interstitial fluid are useful for understanding and management of cancer resistance to immunotherapy. , Monitoring of ion fluxes across membranes of cells or bacteria is a valuable method to study cellular/bacterial physiology and screen ion channel-targeted drugs. , Droplet microfluidics that can be integrated with ion-sensing chemistries may become an enabling platform for these applications. First, ultrasmall-volume samples (pL to nL) can be analyzed in droplet microfluidics, which facilitates tests of bodily fluids secreted at low rates (e.g., saliva) or accessed via invasive procedures (e.g., blood or cerebrospinal fluid) .…”

mentioning

confidence: 99%

Ion-Induced Phase Transfer of Cationic Dyes for Fluorescence-Based Electrolyte Sensing in Droplet Microfluidics

et al. 2021

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Fluorescence-based sensing in droplet microfluidics requires small sample volumes, allows for high-throughput assays, and does not suffer from photobleaching as each flowing sensor is only scanned one time. In this paper, we report a selective and sensitive fluorescence-based ion-sensing methodology in droplet microfluidics using a T-junction PDMS chip. The oil stream is doped with sensor ingredients including an ionophore, a cation exchanger, and a permanently cationic fluorophore as the optical reporter. Electrolyte cations from the aqueous sample are extracted into oil segments and displace the cationic dyes into aqueous droplets. Laser-induced fluorescence of the two immiscible phases is collected alternately, which is in clear contrast to most other ion-selective optode configurations such as nanoparticle suspensions that rely on mixed optical signals of two phases. The cation exchanger, tetrakis[3,5bis(trifluoromethyl)phenyl]borate, is found to dramatically enhance the dye emission in the nonpolar sensing oil by preventing ionpairing interactions and aggregations of the dye molecules, providing new insights into the mechanism of cationic dye-based ion sensors. The high dye brightness allows us to use low concentrations of sensing chemicals (e.g., 10 μM) in the oil and attain high sensitivity for detection of ions in an equal volume of sample. Using valinomycin as the ionophore and methylene blue as the dye, K + is detected with a response time of ∼11 s, a logarithmic linear range of 10 −5 to 10 −2 M, a 20-fold total fluorescence response, >1000fold selectivity against other electrolyte cations, and negligible cross-sensitivity toward the sample pH. The K + concentration in untreated and undiluted whole blood and sweat samples is successfully determined by this microfluidic sensing method without optical interference from the droplet sample to the sensing oil. Detection of other ionic analytes can be achieved using the corresponding ionophores.

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In vivo photoacoustic potassium imaging of the tumor microenvironment

Cited by 15 publications

References 34 publications

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response

Looking deep inside tissue with photoacoustic molecular probes: a review

Ion-Induced Phase Transfer of Cationic Dyes for Fluorescence-Based Electrolyte Sensing in Droplet Microfluidics

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