High-Fidelity Sensitive Tracing Circulating Tumor Cell Telomerase Activity.

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Cancer Research

Background:

• Dynamic tracing of intracellular telomerase activity is vital for cancer diagnosis and therapy.
• Current methods face challenges due to complex reaction systems and inefficient cellular component loading, hindering high-fidelity telomerase activity determination.

Purpose of the Study:

• To develop a novel approach for direct, high-fidelity visualization of intracellular telomerase activity.
• To enable ultrasensitive detection and real-time imaging of telomerase activity in living cancer cells.

Main Methods:

• Development of the Aptamer-Liposome mediated Telomerase activated poly-Molecular beacon Arborescent Nanoassembly (ALTMAN) technique.
• Utilizing molecular beacons that unfold and signal upon telomerase activation, self-assembling into arborescent nanostructures for signal amplification.
• Integration of enzyme-free isothermal signal amplification with a TTAGGG repeat sequence extension for enhanced sensitivity and reduced interference.

Main Results:

• The ALTMAN approach achieved ultrasensitive visualization of activated telomerase with a detection limit of 2 cells·μL⁻¹.
• Real-time imaging of telomerase activity in living cancer cells was successfully demonstrated.
• The method was validated using blood samples from breast cancer patients and urine samples from bladder cancer patients.

Conclusions:

• The ALTMAN approach provides a sensitive and reliable method for visualizing telomerase activity.
• This technique facilitates earlier cancer diagnosis and personalized precision therapy.
• It opens new avenues for telomerase fundamental biological studies and clinical cancer diagnostics.