RESUMO
The advancement of biological imaging techniques critically depends on the development of novel near-infrared (NIR) fluorescent probes. In this study, we introduce a designed NIR fluorescent probe, NRO-ßgal, which exhibits a unique off-on response mechanism to ß-galactosidase (ß-gal). Emitting a fluorescence peak at a wavelength of 670 nm, NRO-ßgal showcases a significant Stokes shift of 85 nm, which is indicative of its efficient energy transfer and minimized background interference. The probe achieves a remarkably low in vitro detection limit of 0.2 U/L and demonstrates a rapid response within 10 min, thereby underscoring its exceptional sensitivity, selectivity, and operational swiftness. Such superior analytical performance broadens the horizon for its application in intricate biological imaging studies. To validate the practical utility of NRO-ßgal in bio-imaging, we employed ovarian cancer cell and mouse models, where the probe's efficacy in accurately delineating tumor cells was examined. The results affirm NRO-ßgal's capability to provide sharp, high-contrast images of tumor regions, thereby significantly enhancing the precision of surgical tumor resection. Furthermore, the probe's potential for real-time monitoring of enzymatic activity in living tissues underscores its utility as a powerful tool for diagnostics in oncology and beyond.
Assuntos
Corantes Fluorescentes , Neoplasias Ovarianas , beta-Galactosidase , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Feminino , beta-Galactosidase/metabolismo , Animais , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Humanos , Linhagem Celular Tumoral , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Imagem Óptica/métodos , Camundongos Nus , Limite de Detecção , Espectrometria de FluorescênciaRESUMO
Three new ergosterols featuring with a highly conjugated ring system, psathrosterols C-E (1-3), have been isolated from the fungus Psathyrella rogueiana. The structures with the absolute configurations were elucidated by means of spectroscopic methods and single crystal X-ray diffraction. Compounds 1-3 exhibit inhibitory activity against NO production with IC50 values ranging from 8.4 to 21.8 µM. Compound 1 inhibits the LPS-induced proliferation of B lymphocyte cells with an IC50 value of 12.3 µM.
Assuntos
Anti-Inflamatórios , Ergosterol , Imunossupressores , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Ergosterol/análogos & derivados , Ergosterol/química , Estrutura Molecular , Camundongos , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Células RAW 264.7 , Óxido Nítrico , Linfócitos B/efeitos dos fármacos , China , Proliferação de Células/efeitos dos fármacosRESUMO
Thyroid cancer always appears insidiously with few noticeable clinical symptoms. Due to its limitations, conventional ultrasound imaging can lead to missed or misdiagnosed cases. Surgery is still the primary treatment method of thyroid cancer, but removal of surrounding healthy tissues to minimize recurrence leads to overtreatment and added patient suffering. To address this challenge, herein, a nitroreductase (NTR) fluorescent probe, Ox-NTR, has been developed for detecting thyroid cancer and tracking the surgical removal of thyroid tumors by fluorescence imaging. The conjugated structure of oxazine 1 was disrupted, significantly reducing the issue of high background signals, thus effectively achieving low background fluorescence. Under hypoxic conditions, the nitro group of Ox-NTR can be reduced to an amine and subsequently decomposed into oxazine 1, emitting intense red fluorescence. Ox-NTR has a low detection limit of 0.09 µg/mL for NTR with excellent photostability and selectivity. Cellular studies show that Ox-NTR can effectively detect NTR levels in hypoxic thyroid cancer cells. Moreover, the ability of Ox-NTR of rapid response to thyroid cancer in vivo is confirmed by fluorescence imaging in mice, distinguishing tumors from normal tissues due to its superior low background fluorescence. Utilizing this fluorescence imaging method during surgical resection can guide the removal of tumors, preventing both missed tumor tissues and accidental removal of healthy tissue. In summary, the novel Ox-NTR offers precise detection capabilities that provide significant advantages over traditional imaging methods for thyroid cancer diagnosis and treatment, making it a valuable tool to guide tumor removal in surgical procedures.