Drug-induced liver injury (DILI) is widely recognized as a major threat to global public health, posing significant obstacles to clinical treatment and drug innovation. The core mechanism underlying DILI progression is the depletion of intracellular glutathione (GSH), which is widely regarded as a key marker of oxidative liver injury and an important biomarker for early-stage DILI. In this study, we developed IC-MAC , a novel near-infrared (NIR) fluorescent probe for the highly sensitive and selective detection of GSH, which exhibited excellent photostability, a large Stokes Shift, and a significant fluorescence enhancement upon reaction with GSH. The probe demonstrated high biocompatibility and enabled real-time imaging of intracellular GSH fluctuations under physiological and oxidative stress conditions. In a mice model of acetaminophen-induced DILI, IC-MAC enabled dynamic visualization of GSH depletion in the liver and its recovery following therapeutic intervention. Fluorescence intensity was significantly correlated with the degree of GSH depletion and treatment response, providing robust evidence for the quantitative assessment of liver injury severity and drug efficacy. Collectively, these findings highlighted the potential of IC-MAC as a powerful platform for early DILI diagnosis and in vivo redox monitoring.
Mesenchymal stem cell-derived exosomes (MSC-Exos) have potential as drug-delivery vehicles and exhibit great promise for hepatocellular carcinoma (HCC) therapy. Here, we consider bone mesenchymal stem cell-derived exosomes (BMSC-Exos) as drug carriers to encase anticancer drug norcantharidin (NCTD) and explore their potential therapeutic effects against HCC. NCTD was loaded into purified exosomes from BMSCs via electroporation, and an in vitro drug release study showed that BMSC-Exos–NCTD provided a continuous and slow release of the drug. A series of in vitro and in vivo pharmacodynamic evaluations based on the HCC cell line HepG2 were conducted. The results showed that the BMSC-Exos–NCTD delivery system effectively promoted cellular uptake, induced cell cycle arrest, reduced tumor cell proliferation, increased apoptosis, and exerted obvious in vivo antitumor effects compared with the NCTD treatment alone, with BMSC-Exos–NCTD showing more significant antitumor effects. Furthermore, the in vivo detection results of the homing effect using the probe Cy5.5 showed that the BMSC-Exos carrier has an in situ homing effect on the tumor sites of HCC in mice. Moreover, BMSC-Exos–NCTD did not show body toxicity. Excitedly, BMSC-Exos–NCTD repaired damaged liver tissues in liver sections; specifically, the experimental effectiveness of the exosomes on the normal liver cell line L02 indicated that the damaged liver cells were repaired by the exosomes, as reflected by the increase in cellular proliferation and the inhibition of liver cell oxidation. Our results suggest that BMSC-Exos, as drug carriers with specific functions, have great potential in the HCC treatment in combination with anticancer drugs.
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