Self-consuming DNA nanogear retrieval exosomes for grading analysis of gliomas.

• A simple and sensitive DNA nanogear sensor has been proposed for grading analysis of gliomas by retrieval exosomes. • The designed DNA nanogear sensor can detect the target exosomes as low as 20 particles/μL. • The gear movement of the sensor on the surface of the exosomes showed a high-gain fluorescence signal. • Dual aptamers targeting exosomes improved the recognition specificity and capture efficiency of the sensor. Direct and accurate analysis of low concentrations of tumor-derived exosomes in complex biological samples is essential for non-invasive cancer diagnosis, but this remains challenging due to the lack of convenient and highly sensitive methods. Herein, we have proposed a novel strategy based on super spherical nucleic acids (SSNAs) combined with nicking enzyme triggering signal amplification for the direct detection of exosomes derived from gliomas. SSNAs utilize AuNPs as carriers, loaded with multifunctional DNA probes. And exosomes are simultaneously labeled by two aptamers. When SSNAs accurately recognize the labeled exosomes, the two make relative gear movement. During the gear movement, the probes act as an exosome-specific retrieval on the one hand, and serves as a fuel that is continuously consumed by the exosomes on the other hand, thus outputting a high-gain fluorescent signal. This strategy exhibits excellent specificity and ultra-high sensitivity for the detection of target exosomes as low as 20 particles/μL. The practicability of this method is further verified by the detection of clinical samples, which retains potential for early glioma diagnosis and grading analysis. [ABSTRACT FROM AUTHOR]