Advances in Organic Small Molecule-Based Fluorescent Probes for Precision Detection of Liver Diseases: A Perspective on Emerging Trends and Challenges

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Liver disease poses a significant challenge to global health, and its early diagnosis is crucial for improving treatment outcomes patient prognosis. Since fluctuation of key biomarkers during the onset progression liver diseases can directly reflect health normal/abnormal function, biomarker-based assays are vital tools detection disease. In this context, small molecule fluorescent probes have undeniably emerged as indispensable analysis, with an ever-growing number molecule-based being developed over recent years, sole aim monitoring relevant This perspective will focus on development application primarily last 10 years diagnosing range disease-related processes. It outline foundational design strategies developing promising probes, their optical response biomarkers, how they been demonstrated in proof-of-concept imaging applications. Current challenges new developments field be discussed, providing insights highlighting opportunities field.

Language: Английский

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Pretargeted Multimodal Tumor Imaging by Enzymatic Self-Immobilization Labeling and Bioorthogonal Reaction

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 12, 2025

Covalent modification of cell membranes has shown promise for tumor imaging and therapy. However, existing membrane labeling techniques face challenges such as slow kinetics poor selectivity cancer cells, leading to off-target effects suboptimal in vivo efficacy. Here, we present an enzyme-triggered self-immobilization strategy, termed E-SIM, which enables rapid selective with bioorthogonal trans-cycloctene (TCO) handles vivo. E-SIM utilizes P-TCO, alkaline phosphatase (ALP) responsive quinone methide (QM) precursor a TCO group, facilitating the conjugation high-density onto via proximity labeling. These groups then react efficiently tetrazine (Tz)-bearing reporters fast reaction, resulting significant enrichment various sizes modalities on membranes. We demonstrate efficacy reaction pretargeted multimodality tumors Notably, achieve efficient installation Tz-modified Renilla luciferase cells vivo, thereby offering highly sensitive bioluminescence signals detecting guiding surgical removal small human HepG2 liver peritoneal metastases. represents robust tool precise complex environments, feasible multimodal applications.

Language: Английский

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Dual-Locked Fluorescence Probe for Monitoring the Dynamic Transition of Pulmonary Macrophages

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Pulmonary macrophages undergo dynamic changes in population, proportion, and polarization during respiratory diseases. Monitoring these is critical for understanding their roles pathology, improving the diagnosis, guiding drug development. However, current analytic methods based on tissue biopsy are invasive static, limiting ability to provide such information. Herein, we report a dual-locked macrophage-specific renal-clearable probe (DMRPNOCas) monitoring of pulmonary influenza A virus (IAV) infection. DMRPNOCas activates fluorescence presence two biomarkers (caspase-1 NO) only coexpressed by M1 macrophages. To optimize NO reactivity, scaffold screened from hemicyanine derivatives with an o-phenylenediamine group positioned differently indole ring. Notably, para-substituted demonstrates higher NO-activated compared its meta-substituted counterpart. This enhancement, as revealed quantum chemical calculations, attributed differential inhibition twisted intramolecular charge transfer induced reaction. specifically distinguishes other leukocytes including T cells, neutrophils, M2 macrophages, capability unmatched single-locked control probes reported probes. Consequently, enables vivo uncovering extensive recruitment monocyte-derived within 48 h IAV process accompanied significant reduction alveolar These findings new insights into macrophage-mediated inflammation underscore potential precise diagnosis pathological processes.

Language: Английский

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Applications of magnetic nanoparticles for boundarics in biomedicine

Fundamental Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Acid Triggering Highly-Efficient Release of Reactive Oxygen Species to Block Mitochondrial-Mediated Homeostasis Maintenance for Accelerating Cell Death

Analytica Chimica Acta, Journal Year: 2025, Volume and Issue: 1340, P. 343645 - 343645

Published: Jan. 11, 2025

Language: Английский

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Dual-Locked Enzyme-Activatable Fluorescence Probes for Precise Bioimaging

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Real-time visualization of endogenous enzymes not only helps reveal the underlying biological principles but also provides pathological information for cancer/disease diagnosis and even treatment guidance. To this end, enzyme-activatable fluorescence probes are frequently fabricated that turn their signals "on" exclusively at enzyme-rich region, thus enabling noninvasive real-time imaging interest molecular level with superior sensitivity selectivity. However, in a complex context, commonly used single (i.e., single-locked) may suffer from "false positive" healthy tissues be insufficient to accurately indicate occurrence certain diseases. Therefore, dual-locked have been promoted address these issues. Using dual (or an enzyme another stimulus) as "keys", they permit simultaneous detection distinct biomarkers, offering significantly enhanced precision toward events. Considering recent reviews on remain scarce, we provide review. We summarize progress, particularly highlighting breakthroughs last three years, discuss challenges field.

Language: Английский

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Small Organic Molecules-based NIR Agents in Cancer Diagnostics: New Frontiers in Imaging and Therapy

Dyes and Pigments, Journal Year: 2025, Volume and Issue: unknown, P. 112648 - 112648

Published: Jan. 1, 2025

Language: Английский

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NIR Fluorescence Strategy for the Early Diagnosis of Melanoma Liver Metastasis Based on the Cascade Reaction of Two Specific Bioenzymes

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Melanoma liver metastasis poses a serious risk to patient health, leading deterioration of function accompanied by symptoms such as jaundice, abdominal pain, and weight loss. Early detection is paramount it allows for timely intervention, potentially improving treatment efficacy outcomes. Herein, dual-target probe activated butyrylcholinesterase (BChE) tyrosinase (TYR) was proposed initiating an enzyme cascade reaction, revealing NIR-emissive methylene blue (MB) responsive product. The reaction mechanism confirmed activity inhibition experiments high-resolution mass spectrometry. Intercellular imaging carried out on the coincubation model Hep G2 B16 cell lines, which first attempt best our knowledge. results showed that BChE expressed in cells TYR overexpressed jointly NIR fluorescence, provides possibility precise melanoma metastasis. In vivo studies further proved this method holds promise early diagnosis postoperative adjunctive therapy hepatic melanoma, ultimately enhancing survival rates.

Language: Английский

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pH-/Viscosity-Activatable NIR Fluorescent Probes via Acceptor Engineering of Hemicyanine Dyes for High-Contrast Bioimaging

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Real-time monitoring of the lysosomal microenvironment using small-molecule probes is critical for understanding complex interactions between organelles and diseases associated with dysfunction. Most traditional fluorescent-dye-based lysosome rely on protonation nitrogen atom in morpholine unit to visualize by inhibiting photoinduced electron transfer (PET) effect. However, these often face selectivity issues within cellular microenvironment. For instance, classic hemicyanine dyes (HD) show nonspecific fluorescence responses liver due inappropriate pKa value, leading low imaging contrast risk false positives. Herein, a series novel pH/viscosity-activatable, lysosomal-targeted near-infrared (NIR) fluorescent were developed incorporating naphthalimide dye dyes. These exhibit no at physiological pH weak under acidic conditions (key 1), substantial activation triggered abnormal viscosity pathological tissues 2). Notably, NpCy-4 demonstrated superior signal-to-background ratio (SBR) proved effective real-time situ diagnosis acute gastritis.

Language: Английский

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Enhancing Clinical Precision in Lung Cancer Tissue Biopsy through Elevated Response-Threshold of an Endoplasmic Reticulum-Targeted Fluorogenic Probe

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101654 - 101654

Published: March 11, 2025

Lung carcinoma is the leading cause of mortality globally, posing a significant public health concern. Fluorescent-mediated tumor imaging emerging as novel diagnostic and therapeutic approach in clinical practice. Nevertheless, traditional probes lack accuracy diagnosing tumors due to overlap baseline values certain biomarkers between normal cells both exhibit turn-on fluorescence, rendering it impossible distinguish tissue from with high resolution. We introduce sensing strategy that constructs probe an elevated biomarker response-threshold targeting ability for endoplasmic reticulum (ER), enabling precise distinction cells, successfully develop such probe. Elevating advantageous minimizing interference cells. Additionally, ER ensures probe's response range consistent content ER, collectively enhancing differentiation cancer Using this probe, distinct bright fluorescence signal could be observed confocal tissues tumor-bearing mice after intravenous injection, stark contrast limited emanating tissues. Furthermore, demonstrated exceptional precision distinguishing lung para-cancer tissue. This work presents more reliable detection strategy, capable accurate diagnosis even when highly expressed It promises valuable tool future applications, particularly intraoperative assisted resection.

Language: Английский

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