Integral Multielement Signals by DNA-Programmed UCNP-AuNP Nanosatellite Assemblies for Ultrasensitive ICP-MS Detection of Exosomal Proteins and Cancer Identification.

Abstract

Exosomes are expected to be used as cancer biomarkers because they carry a variety of cancer-related proteins inherited from parental cells. However, it is still challenging to develop a sensitive, robust, and high-throughput technique for simultaneous detection of exosomal proteins. Herein, three aptamers specific to cancer-associated proteins (CD63, EpCAM, and HER2) are selected to connect gold nanoparticles (AuNPs) as core with three different elements (Y, Eu, and Tb) doped up-conversion nanoparticles (UCNPs) as satellites, thereby forming three nanosatellite assemblies. The presence of exosomes causes specific aptamers to recognize surface proteins and release the corresponding UCNPs, which can be simultaneously detected by inductively coupled plasma-mass spectrometry (ICP-MS). It is worth noting that rare earth elements are scarcely present in living systems, which minimize the background for ICP-MS detection and exclude potential interferences from the coexisting species. Using this method, we are able to simultaneously detect three exosomal proteins within 40 min, and the limit of detection for exosome is 4.7 × 103 particles/mL. The exosomes from seven different cell lines (L-02, HepG2, GES-1, MGC803, AGS, HeLa, and MCF-7) can be distinguished with 100% accuracy by linear discriminant analysis. In addition, this analytical strategy is successfully used to detect exosomes in clinical samples to distinguish stomach cancer patients from healthy individuals. These results suggest that this sensitive and high-throughput analytical strategy based on ICP-MS has the potential to play an important role in the detection of multiple exosomal proteins and the identification of early cancer.