RESUMEN
Whether and how the reactive oxygen species generated by hepatic stellate cells (HSCs) promote immune evasion of hepatocellular carcinoma (HCC) remains mysterious. Therefore, investigating the function of superoxide anion (O2â¢-), the firstly generated reactive oxygen species, during the immune evasion become necessary. In this work, we establish a novel in situ imaging method for visualization of O2â¢- changes in HSCs based on a new two-photon fluorescence probe TPH. TPH comprises recognition group for O2â¢- and HSCs targeting peptides. We observe that O2â¢- in HSCs gradually rose, impairing the infiltration of CD8+ T cells in HCC mice. Further studies reveal that the cyclin-dependent kinase 4 is deactivated by O2â¢-, and then cause the up-regulation of PD-L1. Our work provides molecular insights into HSC-mediated immune evasion of HCC, which may represent potential targets for HCC immunotherapy.
Asunto(s)
Células Estrelladas Hepáticas , Superóxidos , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/inmunología , Animales , Superóxidos/metabolismo , Ratones , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Humanos , Imagen Óptica/métodos , Evasión Inmune , Linfocitos T CD8-positivos/inmunología , Ratones Endogámicos C57BL , Escape del Tumor , MasculinoRESUMEN
The identification and detection of disease-related biomarkers is essential for early clinical diagnosis, evaluating disease progression, and for the development of therapeutics. Possessing the advantages of high sensitivity and selectivity, fluorescent probes have become effective tools for monitoring disease-related active molecules at the cellular level and in vivo. In this review, we describe current fluorescent probes designed for the detection and quantification of key bioactive molecules associated with common diseases, such as organ damage, inflammation, cancers, cardiovascular diseases, and brain disorders. We emphasize the strategies behind the design of fluorescent probes capable of disease biomarker detection and diagnosis and cover some aspects of combined diagnostic/therapeutic strategies based on regulating disease-related molecules. This review concludes with a discussion of the challenges and outlook for fluorescent probes, highlighting future avenues of research that should enable these probes to achieve accurate detection and identification of disease-related biomarkers for biomedical research and clinical applications.
Asunto(s)
Biomarcadores , Colorantes Fluorescentes , Colorantes Fluorescentes/química , Humanos , Biomarcadores/análisis , Biomarcadores/metabolismo , Animales , Neoplasias/diagnóstico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/metabolismo , Inflamación/diagnóstico , Encefalopatías/diagnóstico , Encefalopatías/diagnóstico por imagenRESUMEN
Tumor microenvironment (TME) is the survival environment for tumor cells to proliferate and metastasize in deep tissue. TME contains tumor cells, immune cells, stromal cells and a variety of active molecules including reactive oxygen species (ROS). Inside the TME, ROS regulate the oxidation-reduction (redox) homeostasis and promote oxidative stress. Due to the rapid proliferation ability and specific metabolic patterns of the TME, ROS pervade virtually all complex physiological processes and play irreplaceable roles in protein modification, signal transduction, metabolism, and energy production in various tumors. Therefore, measurements of the dynamically, multicomponent simultaneous changes of ROS in the TME are of great significance to reveal the detailed proliferation and metastasis mechanisms of the tumor. Near-infrared (NIR) and two-photon (TP) fluorescence imaging techniques possess real-time, dynamic, highly sensitive, and highly signal-to-noise ratios with deep tissue penetration abilities. With the rationally designed probes, the NIR and TP fluorescence imaging techniques have been widely used to reveal the mechanisms of how ROS regulates and constructs complex signals and metabolic networks in TME. Therefore, we summarize the design principles and performances of NIR and TP fluorescence imaging of ROS in the TME in the last four years, as well as discuss the advantages and potentials of these works. This Review can provide guidance and prospects for future research work on TME and facilitate the development of antitumor drugs.