Fe–Au Nanoparticle-Coupling for Ultrasensitive Detections of Circulating Tumor DNA

Effectiveness of cancer therapy relies heavily on the efficient early diagnosis. Circulating tumor DNA (ctDNA) detection is one of the most clinically meaningful liquid biopsy approaches for the noninvasive cancer early diagnosis, which, unfortunately, cannot be applied as a routine diagnostic tool till a number of obstacles, for example, unsatisfactory specificity and sensitivity, and extremely high costs, are overcome. Here, the first paradigm of nanomaterial's application in the extremely specific, ultrasensitive, and yet economical ctDNA detections is reported based on a facile nanoparticle-coupling strategy without amplification, with which polymerase chain reaction (PCR)-introduced bias and other shortcomings are successfully circumvented. Aiming at seven Kirsten rat sarcoma-2 virus (KRAS) point mutations, the present strategy exhibits high specificity and an ultrahigh sensitivity of detecting as low as 0.1 pg mL⁻¹ of KRAS point mutation without prior PCR amplification. Discriminating KRAS gene mutations in lung adenocarcinoma patients at an extremely low detection limit equivalent to 0.12% mutation relative to wild-type gene is successful. It is envisioned that this nanoparticle-coupling approach could be routinely applied clinically for ultra-early diagnosis and monitoring of diverse malignant tumors, thus facilitating the fight against cancer.