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Cancer is widely recognized as one of the most devastating diseases, necessitating the development of intelligent diagnostic techniques, targeted treatments, and early prognosis evaluation to ensure effective and personalized therapy. Conventional treatments, unfortunately, suffer from limitations and an increased risk of severe complications. In light of these challenges, boron neutron capture therapy (BNCT) has emerged as a promising approach for cancer treatment with unprecedented precision to selectively eliminate tumor cells. The distinctive and promising characteristics of BNCT hold the potential to revolutionize the field of oncology. However, the clinical application and advancement of BNCT technology face significant hindrance due to the inherent flaws and limited availability of current clinical drugs, which pose substantial obstacles to the practical implementation and continued progress of BNCT. Consequently, there is an urgent need to develop efficient boron agents with higher boron content and specific tumor-targeting properties. Researchers aim to address this need by integrating tumor-targeting strategies with BNCT, with the ultimate goal of establishing BNCT as an effective, readily available, and cutting-edge treatment modality for cancer. This review delves into the recent advancements in integrating tumor-targeting strategies with BNCT, focusing on the progress made in developing boron agents specifically designed for BNCT. By exploring the current state of BNCT and emphasizing the prospects of tumor-targeting boron agents, this review provides a comprehensive overview of the advancements in BNCT and highlights its potential as a transformative treatment option for cancer.
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As a chronic inflammatory disease, rheumatoid arthritis (RA) can cause progressive damage to joints and various organs. Hydrogen peroxide plays a significant role in the pathogenesis and progression of RA and thus serves as a biomarker for diagnosing this disease. Although fluorescent probes have emerged as promising tools for detecting H2O2, most available ones suffer from the aggregation-caused quenching (ACQ) effect, short-wavelength emission, low sensitivity, and poor water solubility. Herein, a new type of "turn-on" AIE probe based on excited state intramolecular proton transfer (ESIPT) was developed, with phenylboronic acid pinacol ester-appended quinolinium as the H2O2 recognition site, which is in the quenched state due to the twisted intramolecular charge transfer (TICT) effect. The probe HTQ-R exhibits good water solubility, high sensitivity, a low detection limit (210 nM), rapid response ability, and good biocompatibility towards hydrogen peroxide, and has shown the ability to accurately target mitochondria. Furthermore, HTQ-R was successfully used to detect exogenous and endogenous hydrogen peroxide in living cells, which enabled real-time monitoring of H2O2 in RA mice, demonstrating its potential significance in the diagnosis and treatment of RA.
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Colorantes Fluorescentes , Protones , Animales , Ratones , Humanos , Peróxido de Hidrógeno , Mitocondrias , Agua , Células HeLaRESUMEN
To facilitate the understanding of the dynamic distribution and activity of lysosomal enzymes, it is highly desirable to develop high-fidelity near-infrared (NIR) activatable fluorescent probes. Here, we propose a general acceptor engineering strategy to construct NIR probes with lysosome-targeting capability. Upon isosteric replacement and additional functionalization, the ß-gal-activatable probe OELyso-Gal exhibited excellent lysosome-targeting capability and favorable responsive performance to the enzyme of interest. Notably, the steric hindrance effect from acceptor engineering is modest, which renders the probe unprecedented affinity to enzymes. Upon the introduction of acceptor engineering, the lysosome-targeting probe became more sensitive to ß-gal in cells and tissues, boosting the discrimination of high ß-gal-expressing ovarian cancer tumours from low ß-gal-expressing tissues. Furthermore, the superiority of OELyso-Gal was validated in real-time visualization of ovarian cancer in tumour-bearing mice. This elegant acceptor engineering strategy provides inspirational insights into the development of customized fluorescent probes for monitoring disease-associated biomarkers within subcellular organelles.
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Excited-state intramolecular proton transfer (ESIPT) has attracted great attention in fluorescent sensors and luminescent materials due to its unique photobiological and photochemical features. However, the current structures are far from meeting the specific demands for ESIPT molecules in different scenarios; the try-and-error development method is labor-intensive and costly. Therefore, it is imperative to devise novel approaches for the exploration of promising ESIPT fluorophores. This research proposes an artificial intelligence approach aiming at exploring ESIPT molecules efficiently. The first high-quality ESIPT dataset and a multi-level prediction system are constructed that realized accurate identification of ESIPT molecules from a large number of compounds under a stepwise distinguishing from conventional molecules to fluorescent molecules and then to ESIPT molecules. Furthermore, key structural features that contributed to ESIPT are revealed by using the SHapley Additive exPlanations (SHAP) method. Then three strategies are proposed to ensure the ESIPT process while keeping good safety, pharmacokinetic properties, and novel structures. With these strategies, >700 previously unreported ESIPT molecules are screened from a large pool of 570 000 compounds. The ESIPT process and biosafety of optimal molecules are successfully validated by quantitative calculation and experiment. This novel approach is expected to bring a new paradigm for exploring ideal ESIPT molecules.
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Environmental problems caused by mercury ions are increasing due to growing industrialization, poor enforcement, and inefficient pollutant treatment. Therefore, detecting and removing mercury from the ecological chain is of utmost significance. Currently, a wide range of small molecules and nanomaterials have made remarkable progress in the detection, detoxification, adsorption, and removal of mercury. In this review, we summarized the recent advances in the design and construction of multifunctional materials, detailed their sensing and removing mechanisms, and discussed with emphasis the advantages and disadvantages of different types of sensors. Finally, we elucidated the problems and challenges of current multifunctional materials and further pointed out the direction for the future development of related materials. This review is expected to provide a guideline for researchers to establish a robust strategy for the detection and removal of mercury ionsin the environment.
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Beta-galactosidase (ß-gal), a typical glycosidase catalyzing the hydrolysis of glycosidic bonds, is regarded as a vital biomarker for cell senescence and cancer occurrence. Given the advantages of high spatiotemporal resolution, high sensitivity, non-invasiveness, and being free of ionizing radiations, fluorescent imaging technology provides an excellent choice for in vivo imaging of ß-gal. In this review, we detail the representative biotech advances of fluorescence imaging probes for ß-gal bearing diverse fidelity-oriented improvements to elucidate their future potential in preclinical research and clinical application. Next, we propose the comprehensive design strategies of imaging probes for ß-gal with respect of high fidelity. Considering the systematic implementation approaches, a range of high-fidelity imaging-guided theragnostic are adopted for the individual ß-gal-associated biological scenarios. Finally, current challenges and future trends are proposed to promote the next development of imaging agents for individual and specific application scenarios.
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Senescencia Celular , Imagen Óptica , beta-Galactosidasa , Colorantes , Glicósido HidrolasasRESUMEN
Chemoresistance remains a huge challenge for effective treatment of non-small cell lung cancer (NSCLC). Previous studies have shown Chinese herbal extracts possess great potential in ameliorating tumor chemoresistance, however, the efficacy is clinically limited mainly because of the poor tumor-targeting and in vivo stability. The construction of nano-delivery systems for herbal extracts has been shown to improve drug targeting, enhance therapeutic efficacy and reduce toxic and side effects. In this study, a folic acid (FA)-modified nano-herb micelle was developed for codelivery of pristimerin (PRI) and paclitaxel (PTX) to enhance chemosensitivity of NSCLC, in which PRI could synergistically enhance PTX-induced growth inhibition of A549 cancer cell. PTX was firstly grafted with the FA-linked polyethylene glycol (PEG) and then encapsulated with PRI to construct the PRI@FA-PEG-PTX (P@FPP) nano-micelles (NMs), which exhibited improved tumor-targeting and in vivo stability. This active-targeting P@FPP NMs displayed excellent tumor-targeting characteristics without obvious toxicity. Moreover, inhibition of tumor growth and metastasis induced by P@FPP NMs were significantly enhanced compared with the combined effects of the two drugs (PRI in combination of PTX), which associated with epithelial mesenchymal transition inhibition to some extent. Overall, this active-targeting NMs provides a versatile nano-herb strategy for improving tumor-targeting of Chinese herbal extracts, which may help in the promotion of enhancing chemosensitivity of NSCLC in clinical applications.