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.