Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry

Kuriki, Yugo; Sogawa, Mari; Komatsu, Toru; Kawatani, Minoru; Fujioka, Hiroyoshi; Fujita, Kyohhei; Ueno, Tasuku; Hanaoka, Kenjiro; Kojima, Ryosuke; Hino, Rumi; Ueo, Hiroki; Ueo, Hiroaki; Kamiya, Mako; Urano, Yasuteru

doi:10.1021/jacs.3c10086

Cited by 8 publications

(1 citation statement)

References 57 publications

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“…A major advantage of targeting active enzymes is the signal amplification due to enzyme-catalyzed turnover. , This characteristic of enzyme-reactive probes enables rapid and high contrast cancer imaging, and various types of fluorescence probes targeting biomarker enzymatic activity have been developed. This Review aims to provide an overview of molecular designs and detection mechanisms of enzyme-reactive fluorescence probes for cancer imaging. …”

Section: Introductionmentioning

confidence: 99%

Activity-Based Fluorescence Diagnostics for Cancer

Fujita,

Urano

2024

Chem. Rev.

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Fluorescence imaging is one of the most promising approaches to achieve intraoperative assessment of the tumor/normal tissue margins during cancer surgery. This is critical to improve the patients' prognosis, and therefore various molecular fluorescence imaging probes have been developed for the identification of cancer lesions during surgery. Among them, "activatable" fluorescence probes that react with cancer-specific biomarker enzymes to generate fluorescence signals have great potential for high-contrast cancer imaging due to their low background fluorescence and high signal amplification by enzymatic turnover. Over the past two decades, activatable fluorescence probes employing various fluorescence control mechanisms have been developed worldwide for this purpose. Furthermore, new biomarker enzymatic activities for specific types of cancers have been identified, enabling visualization of various types of cancers with high sensitivity and specificity. This Review focuses on recent advances in the design, function and characteristics of activatable fluorescence probes that target cancer-specific enzymatic activities for cancer imaging and also discusses future prospects in the field of activity-based diagnostics for cancer. CONTENTS

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Section: Introductionmentioning

confidence: 99%

Activity-Based Fluorescence Diagnostics for Cancer

Fujita,

Urano

2024

Chem. Rev.

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“Zero” Intrinsic Fluorescence Sensing‐Platforms Enable Ultrasensitive Whole Blood Diagnosis and In Vivo Imaging

Jiang,

Liu,

Deng

et al. 2024

Angewandte Chemie

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Abnormal physiological processes and diseases can lead to content or activity fluctuations of biocomponents in organelles and whole blood. However, precise monitoring of these abnormalities remains extremely challenging due to the insufficient sensitivity and accuracy of available fluorescence probes, which can be attributed to the background fluorescence arising from two sources, 1) biocomponent autofluorescence (BCAF) and 2) probe intrinsic fluorescence (PIF). To overcome these obstacles, we have re‐engineered far‐red to NIR II rhodol derivatives that possess weak BCAF interference. And a series of “zero” PIF sensing‐platforms were created by systematically regulating the open‐loop/spirocyclic forms. Leveraging these advancements, we devised various ultra‐sensitive NIR indicators, achieving substantial fluorescence boosts (190 to 1300‐fold). Among these indicators, 8‐LAP demonstrated accurate tracking and quantifying of leucine aminopeptidase (LAP) in whole blood at various stages of tumor metastasis. Furthermore, coupling 8‐LAP with an endoplasmic reticulum‐targeting element enabled the detection of ERAP1 activity in HCT116 cells with p53 abnormalities. This delicate design of eliminating PIF provides insights into enhancing the sensitivity and accuracy of existing fluorescence probes toward the detection and imaging of biocomponents in abnormal physiological processes and diseases.

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Modular Design and Scaffold‐Synthesis of Multi‐Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

Zhang,

Wang,

et al. 2024

Angewandte Chemie

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Fluorophores are essential tools for optical imaging and biomedical research. Their synthetic modification to incorporate new functions, however, remains a challenging task. Conventional strategies rely on linear synthesis in which a parent framework is gradually extended. We here designed and synthesized a versatile library of multi‐functional fluorophores via a scaffold‐based Ugi four‐component reaction (U‐4CR). The adaptability of the scaffold is achieved through modification of starting materials. This allows to use a small range of starting materials for the creation of fluorogenic probes that can detect reactive‐oxygen species and where the localization into subcellular organelles or membranes can be controlled. We present reaction yields ranging from 60 % to 90 % and discovered that some compounds can even function as imaging and therapeutic agents via Fenton chemistry inducing pyroptosis in living cancer cells. Our study underlines the potential of scaffold‐based synthesis for versatile creation of functional fluorophores and their applications.

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Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry

Cited by 8 publications

References 57 publications

Activity-Based Fluorescence Diagnostics for Cancer

Activity-Based Fluorescence Diagnostics for Cancer

“Zero” Intrinsic Fluorescence Sensing‐Platforms Enable Ultrasensitive Whole Blood Diagnosis and In Vivo Imaging

Modular Design and Scaffold‐Synthesis of Multi‐Functional Fluorophores for Targeted Cellular Imaging and Pyroptosis

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