Bienzyme-Locked Activatable Fluorescent Probes for Specific Imaging of Tumor-Associated Mast Cells

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(18), С. 12656 - 12663

Опубликована: Апрель 29, 2024

Tumor-associated mast cells (TAMCs) have been recently revealed to play a multifaceted role in the tumor microenvironment. Noninvasive optical imaging of TAMCs is thus highly desired gain insights into their functions cancer immunotherapy. However, due lack single enzyme that specific cells, common probe design approach based on single-enzyme activation not applicable. Herein, we reported bienzyme-locked molecular (THCMC) photoinduced electron transfer-intramolecular charge-transfer hybrid strategy for vivo TAMCs. The mechanism ensures THCMC exclusively turns near-infrared (NIR) fluorescence only presence both tryptase and chymase specifically coexpressed by cells. Thus, effectively distinguishes from other leukocytes, including T neutrophils, macrophages, capability lacking single-locked probes. Such high specificity allows noninvasive tracking fluctuation living mice during results reveal decreased intratumoral signal after combination immunotherapy correlates well with reduced population TAMCs, accurately predicting inhibition growth. this study presents first NIR fluorescent but also proposes generic cell imaging.

Язык: Английский

---

Dual‐Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High‐Precision Imaging of Tumor Boundaries

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(32)

Опубликована: Май 23, 2024

Clear delineation of tumor margins is essential for accurate resection and decreased recurrence rate in the clinic. Fluorescence imaging emerging as a promising alternative to traditional visual inspection by surgeons intraoperative imaging. However, probes lack accuracy diagnosis, making it difficult depict boundaries accurately. Herein, we proposed an offensive defensive integration (ODI) strategy based on "attack systems (invasive peptidase) defense (reductive microenvironment)" multi-dimensional characteristics design activatable fluorescent precisely. Screened out from series ODI strategy-based probes, ANQ performed better than unilateral correlation distinguishing between cells normal minimizing false-positive signals living metabolic organs. To further improve signal-to-background ratio vivo, derivatized FANQ, was prepared successfully applied distinguish orthotopic hepatocellular carcinoma tissues adjacent mice models clinical samples. This work highlights innovative develop rapid diagnosis tumors high-precision boundaries, providing more efficient tools future applications assisted resection.

Язык: Английский

---

Dual-Locked Enzyme-Activatable Bioorthogonal Fluorescence Turn-On Imaging of Senescent Cancer Cells

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22689 - 22698

Опубликована: Авг. 5, 2024

Bioorthogonal pretargeting optical imaging shows the potential for enhanced diagnosis and prognosis. However, bioorthogonal handles, known being "always reactive", may engage in reactions at unintended sites with their counterparts, resulting nonspecific fluorescence activation diminishing detection specificity. Meanwhile, despite importance of detecting senescent cancer cells therapy, current methods mainly rely on common single senescence-associated biomarkers, which lack specificity differentiating between various types cells. Herein, we report a dual-locked enzyme-activatable (DEBOF) turn-on approach specific A targeting agent (DBTA) bioorthogonally activatable fluorescent probe (BAP) are synthesized as biorthogonal pair. DBTA is tetrazine derivative dually caged by two enzyme-cleavable moieties, respectively, associated senescence cancer, ensures that its reactivity ("clickability") only triggered presence BAP fluorophore trans-cyclooctane (TCO), whose activated upon reaction TCO decaged DBTA. As such, DEBOF differentiates from nonsenescent or other cells, allowing noninvasive tracking population fluctuation tumor living mice to guide therapies. This study thus provides general molecular strategy biomarker-activatable vivo be applied modalities beyond optics.

Язык: Английский

---

Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Сен. 13, 2024

Язык: Английский

---

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(4), С. 1238 - 1255

Опубликована: Янв. 1, 2024

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level.Among these modifications, N7-methylguanosine (m7G) stands out as one of most prevalent.Over recent years, significant attention has been directed towards understanding implications m7G modification.This modification is present diverse molecules, including transfer RNAs, messenger ribosomal other noncoding RNAs.Its regulation occurs through series specific methyltransferases m7G-binding proteins.Notably, implicated various diseases, prominently across multiple cancer types.Earlier studies have elucidated significance context immune within tumor microenvironment.This comprehensive review culminates synthesis findings related to modulation cells infiltration, encompassing T cells, B innate all orchestrated modification.Furthermore, interplay between its regulatory proteins can profoundly affect efficacy adjuvant therapeutics, thereby potentially serving biomarker therapeutic target for combinatory interventions types.

Язык: Английский

---

Nitrile-aminothiol bioorthogonal near-infrared fluorogenic probes for ultrasensitive in vivo imaging

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 2, 2025

Bioorthogonal chemistry-mediated self-assembly holds great promise for dynamic molecular imaging in living organisms. However, existing approaches are limited to nanoaggregates with 'always-on' signals, suffering from high signal-to-background ratio (SBR) and compromised detection sensitivity. Herein we report a nitrile-aminothiol (NAT) bioorthogonal fluorogenic probe (CyNAP-SS-FK) ultrasensitive diagnosis of orthotopic hepatocellular carcinoma. This comprises nitrile-substituted hemicyanine scaffold cysteine tail dually locked biomarker-responsive moieties. Upon dual cleavage by tumor-specific cathepsin B biothiols, the 1,2-aminothiol residue is exposed spontaneously reacts nitrile group situ intramolecular macrocyclization, enabling near-infrared fluorescence (NIRF) turn-on as well self-assembly. In male mice, such 'cleavage-click-assembly' regimen allows real-time small cancerous lesions (~2 mm diameter) improved SBR (~5) extended window (~36 h), outperforming conventional clinical assays. study not only presents NAT click reaction-based probes but also highlights generic dual-locked design these probes. Existing can suffer low Here, authors sensing action lesions.

Язык: Английский

---

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

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

---

Molecular probes for in vivo optical imaging of immune cells

Nature Biomedical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Язык: Английский

---

Inserting “OFF-to-ON” BODIPY Tags into Cytokines: A Fluorogenic Interleukin IL-33 for Real-Time Imaging of Immune Cells

ACS Central Science, Год журнала: 2023, Номер 10(1), С. 143 - 154

Опубликована: Дек. 20, 2023

The essential functions that cytokine/immune cell interactions play in tissue homeostasis and during disease have prompted the molecular design of targeted fluorophores to monitor their activity real time. Whereas activatable probes for imaging immune-related enzymes are common, many immunological mediated by binding events between cytokines cognate receptors hard live-cell imaging. A prime example is interleukin-33 (IL-33), a key cytokine innate adaptive immunity, whose interaction with ST2 cell-surface receptor results downstream signaling activation NF-κB AP-1 pathways. In present work, we designed chemical platform site-specifically introduce OFF-to-ON BODIPY into full proteins generate first nativelike fluorescent analogues IL-33. Among different incorporation strategies, aminoacylation followed bioorthogonal derivatization led best labeling results. Importantly, BODIPY-labeled IL-33 derivatives─unlike IL-33-GFP constructs─exhibited ST2-specific bioactivity profiles comparable those wild-type interleukin. Real-time fluorescence microscopy assays under no wash conditions confirmed internalization through its intracellular trafficking endosomal pathway. We envision modularity versatility our will facilitate synthesis minimally tagged fluorogenic as next generation reagents real-time visualization live immune cells.

Язык: Английский

---

Dual‐Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High‐Precision Imaging of Tumor Boundaries

Angewandte Chemie, Год журнала: 2024, Номер 136(32)

Опубликована: Май 23, 2024

Abstract Clear delineation of tumor margins is essential for accurate resection and decreased recurrence rate in the clinic. Fluorescence imaging emerging as a promising alternative to traditional visual inspection by surgeons intraoperative imaging. However, probes lack accuracy diagnosis, making it difficult depict boundaries accurately. Herein, we proposed an offensive defensive integration (ODI) strategy based on “attack systems (invasive peptidase) defense (reductive microenvironment)” multi‐dimensional characteristics design activatable fluorescent precisely. Screened out from series ODI strategy‐based probes, ANQ performed better than unilateral correlation distinguishing between cells normal minimizing false‐positive signals living metabolic organs. To further improve signal‐to‐background ratio vivo, derivatized FANQ , was prepared successfully applied distinguish orthotopic hepatocellular carcinoma tissues adjacent mice models clinical samples. This work highlights innovative develop rapid diagnosis tumors high‐precision boundaries, providing more efficient tools future applications assisted resection.

Язык: Английский

---