Universal Ti3C2 MXenes Based Self-Standard Ratiometric Fluorescence Resonance Energy Transfer Platform for Highly Sensitive Detection of Exosomes

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)/Ti₃C₂ 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 Ti₃C₂ 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 Ti₃C₂ 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 × 10³ 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.