Viscosity-Tuned Mitochondrial Probe for Precision Tumor Theranostics and Apoptosis Imaging

Abstract

Early cancer diagnosis greatly enhances survival rates and improves patients’ quality of life. Intracellular viscosity, among various microenvironmental factors influencing cellular function, plays a pivotal role. Abnormal viscosity levels are closely linked to cancer progression, impacting biomolecular diffusion, metabolic activity, and signal transduction. Monitoring and understanding changes in intracellular viscosity could offer valuable insights into early cancer detection and therapeutic strategies. Notably, increased mitochondrial viscosity is associated with malignant tumor development. Since mitochondria play a key role in cancer, studying their function, especially in mitophagy (mitochondrial recycling) and apoptosis (programmed cell death), is crucial for cancer research and treatment. Herein, we report a fluorescent probe with large Stokes shifts designed for mitochondrial viscosity imaging. The probe features an indolium iodide moiety for enhanced mitochondrial targeting and a 2-chlorocyclohex-1-ene-1-carbaldehyde group to extend emission wavelengths. Mito-BCy exhibits a viscosity-dependent fluorescence turn-on at 635 nm, with a linear response ranging from 0.89 to 945 cP. Using Mito-BCy, we successfully monitored mitochondrial viscosity changes in live cells under LPS, OA, and nystatin treatment. Furthermore, the probe enabled real-time imaging of mitochondrial viscosity variations during mitophagy (starvation-induced) and apoptosis (cisplatin-induced) at the cellular level. Meanwhile, Mito-BCy successfully detected dynamic fluctuations of viscosity in zebrafish animal models. Importantly, Mito-BCy revealed elevated mitochondrial viscosity in tumor tissues compared with normal tissues. Furthermore, it enabled dynamic monitoring of therapeutic responses, highlighting its potential as a powerful tool for evaluating cancer treatment efficacy.

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