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Viscosity-Tuned Mitochondrial Probe for Precision Tumor Theranostics and Apoptosis Imaging
Jialu Tian1, Lixia Zhang1, Yanchun Qiao1
1Affiliated Hospital of Shandong Second Medical University (261031, School of Clinical Medicine), School of Pharmacy, Shandong Second Medical University, Weifang 261053, People's Republic of China.
Analytical Chemistry
|July 8, 2025
Summary
A new fluorescent probe, Mito-BCy, enables precise measurement of intracellular viscosity, crucial for early cancer detection. This tool monitors mitochondrial viscosity changes in cells and zebrafish, revealing elevated levels in tumors and tracking treatment responses.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Cancer Research
Background:
- Intracellular viscosity is a key microenvironmental factor affecting cellular functions like diffusion and metabolism.
- Abnormal intracellular viscosity is linked to cancer progression, impacting biomolecular diffusion, metabolic activity, and signal transduction.
- Mitochondrial viscosity changes are associated with malignant tumor development, making them critical targets for cancer research.
Purpose of the Study:
- To develop and characterize a novel fluorescent probe for sensitive and specific imaging of intracellular viscosity.
- To investigate the role of mitochondrial viscosity in cellular processes relevant to cancer, including mitophagy and apoptosis.
- To evaluate the probe's utility in detecting cancer-related viscosity changes in vitro, in vivo, and in response to therapy.
Main Methods:
- Design and synthesis of a novel fluorescent probe (Mito-BCy) with a large Stokes shift for mitochondrial viscosity imaging.
- Characterization of Mito-BCy's fluorescence response to viscosity variations (0.89–945 cP) with a linear turn-on at 635 nm.
- Application of Mito-BCy for real-time monitoring of mitochondrial viscosity in live cells, zebrafish models, and tumor tissues.
Main Results:
- Mito-BCy demonstrated a viscosity-dependent fluorescence turn-on, enabling quantitative intracellular viscosity measurements.
- The probe successfully monitored mitochondrial viscosity changes induced by various treatments (LPS, OA, nystatin) in live cells.
- Mito-BCy effectively imaged dynamic viscosity variations during mitophagy and apoptosis, and detected elevated mitochondrial viscosity in tumor tissues compared to normal tissues.
- The probe facilitated real-time monitoring of therapeutic responses in preclinical models.
Conclusions:
- Mito-BCy is a powerful fluorescent tool for accurate and dynamic imaging of intracellular viscosity, particularly in mitochondria.
- Monitoring mitochondrial viscosity using Mito-BCy offers valuable insights into early cancer detection and progression.
- This probe holds significant potential for evaluating cancer treatment efficacy and guiding therapeutic strategies.
