RESUMEN
Despite the apparent copious fluorescent probes targeting mitochondria, the development of low cytotoxic probes is still needed for improving validation of mitochondrial function assessment. Herein, we report a novel cyanine-based NIR fluorescent probe, T2, which selectively targets mitochondria with significantly low toxicity by modulating the intracellular redox status. Additionally, T2 inhibits oxidative stress-induced cell death in cortical neurons. This study provides new insight into developing low-toxic mitochondrial imaging agents by regulating redox homeostasis.
Asunto(s)
Diagnóstico por Imagen , Estrés Oxidativo , Muerte Celular , Oxidación-Reducción , Colorantes Fluorescentes/toxicidad , Colorantes Fluorescentes/metabolismo , Mitocondrias/metabolismoRESUMEN
A new conjugate formulation, SIWV-PB-SN, based on glioblastoma (GBM)-homing SIWV tetrapeptide and an ROS-responsive prodrug is reported. SIWV-PB-SN selectively penetrates the GBM cells and releases anti-GBM drug (SN-38) via ROS-induced linker cleavage. This study presents a new insight for a more advanced therapeutic approach to overcoming GBM.
Asunto(s)
Glioblastoma , Profármacos , Línea Celular Tumoral , Glioblastoma/tratamiento farmacológico , Humanos , Irinotecán , Profármacos/farmacología , Profármacos/uso terapéutico , Especies Reactivas de OxígenoRESUMEN
Peroxynitrite (ONOO- ) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO- influx in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was designed by a structure-modulated strategy. Taking advantage of ONOO- -initiated two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO- in 0.3â mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F0 =50). Moreover, with its mitochondria-targeting ability, Rd-DPA3 can be used to efficiently monitor the alternations of intracellular ONOO- levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood-brain barrier (BBB) crossing ability, Rd-DPA3 is suitable for in vivo imaging of cerebral ONOO- influx and illustrating an age-dependent accumulation of ONOO- in AD mice brains.
