Exosomes, as novel noninvasive biomarkers for disease prediction and diagnosis, have shown fascinating prospects in monitoring cancer-linked public health issues. Herein, a unique Cy3 labeled CD63 aptamer (Cy3-CD63 aptamer)/Ti 3 C 2 MXenes nanocomplex was constructed as a self-standard ratiometric fluorescence resonance energy transfer (FRET) nanoprobe for quantitative detection of exosomes. The Cy3-CD63 aptamer can be selectively adsorbed onto the Ti 3 C 2 MXene nanosheets by hydrogen bond and metal chelate interaction between the aptamer and MXenes, and the fluorescence signal from Cy3-CD63 aptamer was quenched quickly owing to the FRET between the Cy3 and MXenes. The fluorescence of Cy3 greatly recovered after the addition of the exosomes which can specifically combine with the aptamer and release from the surface of Ti 3 C 2 MXenes due to the high affinity between the aptamer and CD63 protein on exosome surface. Meanwhile, the self-fluorescence signal of MXenes in the whole process showed little change, which can be used as a standard reference. Based on the self-standard turn-on FRET biosensing platform the detection limit of exosome was determined as 1.4 × 10 3 particles mL −1 , which was over 1000× lower than that of conventional ELISA method. This fluorescence sensor can also be used for the identification of multiple biomarkers on the exosome surface and different kinds of exosomes, combining with the fluorescent confocal scanning microscope image. The proposed strategy not only provides a universal nanoplatform for exosomes, but also can be extensively expanded to multiple biomarkers detection, which may promise the prospect of MXenes as robust candidates in biological fields.
Photoacoustic (PA) imaging, as a fast growing technology that combines the high contrast of light and large penetration depth of ultrasound, has demonstrated great potential for molecular imaging of cancer. However, PA molecular imaging of orthotopic brain tumors is still challenging, partially due to the limited options and insufficient sensitivity of available PA molecular probes. Here, the direct formation of single-layer (S-MoS 2 ), few-layer (F-MoS 2 ), and multi-layer (M-MoS 2 ) nanosheets by the albumin-assisted exfoliation without further surface modifications is reported. It is demonstrated that the PA effect of the MoS 2 nanosheets is highly dependent on their layered nanostructures. Decreasing the number of nanosheet layers from M-MoS 2 to S-MoS 2 can both significantly enhance the near-infrared light absorption and improve the elastic properties of the nanomaterial, resulting in greatly amplified PA effect. The in vitro experiments demonstrate that the prepared S-MoS 2 with excellent biocompatibility can be efficiently internalized into U87 glioma cells, producing strong PA signals for highly sensitive detection of brain tumor cells, with a detection limit of ≈100 cells. Intravenous administration of S-MoS 2 to both U87 subcutaneous and orthotopic tumor-bearing mice shows highly efficient tumor retention and significantly enhanced PA contrast. Tumor tissue ≈1.5 mm below the skull can still be clearly visualized in vivo. Previous studies suggest that the fabricated S-MoS 2 with amplified PA effect have high potential to serve as an efficient nanoplatform for sensitive PA molecular imaging and hold promising prospect for translational medicine.
In
this work, an ultrasensitive electrogenerated chemiluminescence
(ECL) biosensor for exosomes and their surface proteins was developed
by the in situ formation of gold nanoparticles (AuNPs) decorated Ti3C2 MXenes hybrid with aptamer modification (AuNPs-MXenes-Apt).
In this strategy, the exosomes were efficiently captured on an exosome
recognized CD63 aptamer modified electrode interface. Meanwhile, in
situ formation of gold nanoparticles on single layer Ti3C2MXenes with aptamer (MXenes-Apt) modification was obtained,
in which MXenes acted as both reductants and stabilizer, and no additional
reductant and stabilizer involved. The in situ formed AuNPs-MXenes-Apt
hybrid not only presented highly efficient recognition of exosomes
specifically, but also provide naked catalytic surface with high electrocatalytic
activity of gold nanoparticles with predominated (111) facets that
significantly improved the ECL signal of luminol. In this way, a highly
sensitive ECL biosensor for exosomes detection was constructed ascribing
to the synergistic effects of large surface area, excellent conductivity,
and catalytic effects of the AuNPs-MXenes-Apt. The detection limit
is 30 particles μL–1 for exosomes derived
from HeLa cell line, which was over 1000 times lower than that of
conventional ELISA method and the linear range was from 102 particles μL–1 to 105 particles
μL–1. This ECL sensing platform possessed
high selectivity toward exosomes and their surface proteins derived
different kinds of tumor cell lines (HeLa cells, OVCAR cells and HepG2
cells), and enabled sensitive and accurate detection of exosomes from
human serum, which implied that the ECL biosensor provided a feasible,
sensitive, and reliable tool for exosomes detection in exosomes-related
clinical diagnostic.
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