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A fluorescence quenching mechanism using linear diselenides was proposed for the first time through a combination of intramolecular charge transfer (ICT) and Förster resonance energy transfer (FRET). Herein, we synthesized and screened a two-photon fluorescent probe AFC-SeSe, demonstrating a remarkable 300-fold increase in response to glutathione (GSH). Additionally, AFC-SeSe enabled real-time observation of increased thiol levels following treatment within a short timeframe in a mouse model of stroke. [ABSTRACT FROM AUTHOR]

Vicinal dithiol proteins (VDPs) facilitate cellular redox homeostasis, modulate protein synthesis and participate in post-translational modifications through the dynamic equilibrium of dithiol and disulfide bonds. Herein, an activatable red emitting fluorescent probe, VDP-red, is developed for detecting VDPs. With the aid of this probe, we have discovered for the first time a reduction in the levels of reduced VDPs in a stroke mouse model. This work provides a fresh viewpoint for understanding stroke mechanisms. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) poses a risk for numerous metabolic diseases. To date, the U.S. Food and Drug Administration has not yet approved any medications for the treatment of NAFLD, for which developing therapeutic drugs is urgent. Dihydromyricetin (DMY), the most abundant flavonoid in vine tea, has been shown to be hepatoprotective. Its application was limited by low bioavailability in vivo; Methods: In order to improve the bioavailability of DMY and achieve liver-targeted delivery, we designed a DMY-loaded stiff-soft hybrid biomimetic nano drug delivery system (DMY-hNE). The in vivo absorption, distribution, pharmacokinetic profiles, and anti-NAFLD efficacy of DMY-hNE were studied; Results: DMY-hNE was composed of a stiff core and soft shell, which led to enhanced uptake by gastrointestinal epithelial cells and increased penetration of the mucus barrier, thus improving the in vivo absorption, plasma DMY concentration, and liver distribution versus free DMY. In an early NAFLD mouse model, DMY-hNE effectively ameliorated fatty lesions accompanied with reduced lipid levels and liver tissue inflammation; Conclusions: These findings suggested that DMY-hNE is a promising platform for liver drug delivery and treatment of hepatopathy. [ABSTRACT FROM AUTHOR]

The burgeoning prodrug strategy offers a promising avenue toward improving the efficacy and specificity of cytotoxic drugs. Elevated intracellular levels of glutathione (GSH) have been regarded as a hallmark of tumor cells and characteristic feature of the tumor microenvironment. Considering the pivotal involvement of elevated GSH in the tumorigenic process, a diverse repertoire of GSH‐triggered prodrugs has been developed for cancer therapy, facilitating the attenuation of deleterious side effects associated with conventional chemotherapeutic agents and/or the attainment of more efficacious therapeutic outcomes. These prodrug formulations encompass a spectrum of architectures, spanning from small molecules to polymer‐based and organic–inorganic nanomaterial constructs. Although the GSH‐triggered prodrugs have been gaining increasing interests, a comprehensive review of the advancements made in the field is still lacking. To fill the existing lacuna, this review undertakes a retrospective analysis of noteworthy research endeavors, based on a categorization of these molecules by their diverse recognition units (i.e., disulfides, diselenides, Michael acceptors, and sulfonamides/sulfonates). This review also focuses on explaining the distinct benefits of employing various chemical architecture strategies in the design of these prodrug agents. Furthermore, we highlight the potential for synergistic functionality by incorporating multiple‐targeting conjugates, theranostic entities, and combinational treatment modalities, all of which rely on the GSH‐triggering. Overall, an extensive overview of the emerging field is presented in this review, highlighting the obstacles and opportunities that lie ahead. Our overarching goal is to furnish methodological guidance for the development of more efficacious GSH‐triggered prodrugs in the future. By assessing the pros and cons of current GSH‐triggered prodrugs, we expect that this review will be a handful reference for prodrug design, and would provide a guidance for improving the properties of prodrugs and discovering novel trigger scaffolds for constructing GSH‐triggered prodrugs. [ABSTRACT FROM AUTHOR]