Ultrasensitive Telomerase Activity Detection in Circulating Tumor Cells Based on DNA Metallization and Sharp Solid-State Electrochemical Techniques

Being considered a liquid biopsy, circulating tumor cell (CTC) quantification is of great interest for evaluating cancer dissemination, predicting patient prognosis, and also for the evaluation of therapeutic treatments, representing a reliable potential alternative to invasive biopsies and subsequent proteomic and functional genetic analysis. Compared to a biopsy, the gold standard of current cancer diagnosis, an important characteristic of a blood test is that it is safe and can be performed at many points during the disease, allowing the development of appropriate therapy modifications and potentially improving patient's quality of life. In this work, an ultrasensitive electrochemical telomerase activity-sensing strategy is presented that utilizes DNA-templated deposition of silver nanoparticles as electroactive labels through a highly sharp solid-state Ag/AgCl reaction with DNA exonuclease III-assisted background current suppression. This nanoparticle-mediated signal amplification resulted in significantly decreased detection limit, which is better than the vast majority of reported methods and achieves a sensitivity comparable to the conventional telomeric repeat amplification protocol (TRAP). This work may pave a new PCR-free way for the detection of telomerase activity in CTCs via a noninvasive routine blood test for point-of-care diagnosis and individualized treatment of cancer