The Dual-Response–Single-Amplification Fluorescent Nanomachine for Tumor Imaging and Gastric Cancer Diagnosis

Gastric cancer (GC) is one of the most common tumors worldwide and is the leading cause of tumor-related mortality. Traditional biomarkers and screening methods cannot meet the clinical demands. There is an urgent need for highly sensitive diagnostic markers as well as accurate quantification methods for early gastric cancer (EGC) screening. Here a dual-target cooperatively responsive fluorescent nanomachine by the innovative application of two targets─responsive strand migration system with a single-amplification-cycle element was developed for the simultaneous detection of GC biomarkers miR-5585-5p and PLS3 mRNA, which were selected by next-generation sequencing and RT-qPCR. It was also an RNA extraction-free, PCR-free, and nonenzymatic biosensor to achieve tumor cell imaging and serum diagnosis. Requiring only a 20 μL serum sample and 20 min incubation time, the nanomachine achieved an ultrasensitive detection limit of fM level with a broad linear range from fM to nM. More importantly, a higher AUC value (0.884) compared to the clinically used biomarker CA 72-4 was obtained by the nanomachine to distinguish GC patients successfully. Notably, for the key concerns of diagnosis of EGC patients, the nanomachine also achieved a satisfactory AUC value of 0.859. Taken together, this work has screened and obtained multiple biomarkers and developed a fluorescent nanomachine for combination diagnosis of GC, providing an ingenious design of a functionalized DNA nanomachine and a feasible strategy for the transformation of serum biomarkers into clinical diagnosis.