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Tumor Microenvironment-Activated Ultrasensitive Nanoprobes for Specific Detection of Intratumoral Glutathione by Ratiometric Photoacoustic Imaging

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TLDR
A novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors.
Abstract
Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellular functions. Precise quantification of GSH via advanced noninvasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable near-infrared spectroscopy (NIR) absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors. This special ratiometric PAI nanoprobe (CR-POM) is synthesized through the self-assembly of croconaine (CR) dye and molybdenum-based polyoxometalate (POM) clusters with opposite NIR absorbance change in response to GSH. The resulting amplified ratiometric absorbance (Ab866/Ab700), the relatively low limit of detection value (0.51 mM), and the unique acidity-activated self-aggregation contribute to the prolonged intratumoral retention and enhanced tumor accumulation of CR-POM for accurate quantification of intratumoral GSH (0.5-10 mM). Featuring the additional merit of 64Cu radiolabeling for whole-body positron-emission tomography imaging, the smartly designed CR-POM nanoprobe will open new horizons for real-time noninvasive monitoring of biodistribution and simultaneous accurate quantification of GSH levels, especially in tumor and other GSH-related pathophysiological processes.

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Citations
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Fluorescent-based nanosensors for selective detection of a wide range of biological macromolecules: A comprehensive review.

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Chemical Design of Activatable Photoacoustic Probes for Precise Biomedical Applications.

TL;DR: In this article , a review of the recent developments of activatable photoacoustic (PA) probes for precise biomedical applications including molecular detection of the biotargets and imaging of the biological events is presented.
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Colorimetric and fluorescent detection of glutathione over cysteine and homocysteine with red-emitting N-doped carbon dots

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Highly photostable croconium dye-anchored cell membrane vesicle for tumor pH-responsive duplex imaging-guided photothermal therapy.

TL;DR: Highly photostable amphiphilic croconium dye-anchored red blood cell membrane vesicle is developed for tumor pH-responsive near-infrared fluorescence (NIRF) and photoacoustic (PA) duplex imaging-guided photothermal therapy for cancer theranostics.
References
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Journal ArticleDOI

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Journal ArticleDOI

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Semiconducting polymer nanoparticles as photoacoustic molecular imaging probes in living mice

TL;DR: Near infrared (NIR) light absorbing semiconducting polymer nanoparticles (SPNs) are introduced as a new class of contrast agents for PA molecular imaging and demonstrate SPNs an ideal nanoplatform for developing PA molecular probes.
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