Molecular filling and metal ion-mediated DNA self-assembly strategy enable evaluation of lung cancer metastasis

Accurately assessing the risk of lung cancer metastasis is crucial for improving patient prognosis and quality of life. In this study, we developed a rapid, homogeneous fluorescence detection system (DNA-N@Ag⁺@PIX) for lung cancer mesenchymal circulating tumor cells (M-CTCs) based on a molecular filling strategy and metal ion-mediated DNA self-assembly. By introducing small molecules such as pixantrone dimaleate (PIX) as molecular fillers, the stability of the DNA nanomaterials and the detection sensitivity of the detection system were significantly improved. The constructed DNA-N@Ag⁺@PIX system employed vimentin as a marker. Specific target-aptamer binding triggered the depolymerization of the DNA nanostructure and the release of Ag⁺, which was subsequently transduced into a fluorescence signal using CdTe quantum dots (QDs), thereby enabling ultrasensitive detection of M-CTCs in the peripheral blood of patients with non-small cell lung cancer. The system completed detection within 30 min, and the detection limit reached the single cell level. Analysis of 60 clinical samples demonstrated that the system could effectively distinguish non-metastatic and metastatic patients, achieving high specificity (91.9%) and sensitivity (95.7%), and the results were consistent with clinical diagnosis. This study provided an effective liquid biopsy strategy for monitoring lung cancer metastasis risk.