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

Abstract

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.

Interaction of single- and double-stranded DNA with multilayer MXene by fluorescence spectroscopy and molecular dynamics simulations

“…In the case of ssDNA labeled by FAM, the uorophore interacted mainly with the surface, whereas in the case of dsDNA the FAM not only interacted with the surface but also with the end of the double helix by stacking. These observations can explain the quenched uorescence of ssDNA which has also been evidenced in recent works, 37,58 and can be assigned to resonant electron transfer given the spectral overlap and the low-range distance. But given the low distance (#10Å), the question of whether Dexter energy transfer has a role also arises.…”

“…[32][33][34][35] Very recently, a nanopore DNA sequencing system has been reported with MXene membranes. 36 Aptamer-based assays have also been recently developed for exosome detection, 37,38 as well as MXene composites with DNA for dopamine detection. 39 Herein, we probe the interaction between single-and double-stranded DNA with Ti 3 C 2 T x , the most studied and widely used MXene, by means of uorescence spectroscopy and molecular dynamics (MD) simulations.…”

Applications of Bionano Sensor for Extracellular Vesicles Analysis

“…As a result, the quenched fluorescent signal linearly correlated to the concentration range of 1.0 × 10 4 -1.0 × 10 8 EVs/µL and reached a LOD of down to 1.1 × 10 3 EVs/µL. Lee et al developed a selective and sensitive system to detect exosomal miRNA ( Figure 2D) by using the quenching and recovery of fluorescence mechanism, as well as the metal-enhanced fluorescence of a multifunctional single nanorod structure with magnetic and plasmonic components [63]. Each component was specifically modified to selectively isolate targeted EVs through magnetic immunoseparation and sensitively and selectively identify targeted exosomal miRNA using a fluorophore-labeled hairpin single-stranded molecular beacon.…”

Exosomes as a Source of Cancer Biomarkers: Advances in Electrochemical Biosensing of Exosomes

“…The biosensor exhibited an excellent performance by analysis of spiked serum samples with recovery indices from 95 % to 104 % . In the next study from the same group, it was shown that, besides CD63 and EpCAM, other proteins present on the surface of the exosome can be targeted by DNA aptamers, including PSMA and PTK‐7 . Another MXene‐based biosensor for the detection of exosomes was studied by Fang et al .…”