An Electrochemical Biosensor Designed by Using Zr-Based Metal–Organic Frameworks for the Detection of Glioblastoma-Derived Exosomes with Practical Application

Abstract

Glioblastoma (GBM) is one of the most fatal tumors in the brain, and its early diagnosis remains technically challenging due to the complex repertoires of oncogenic alterations and blood-brain barrier (BBB). GBM-derived specific exosomes can cross the BBB and circulate in body fluids, so they can be noninvasive biomarkers for the early diagnosis of GBM. Herein, we propose a sensitive and label-free electrochemical biosensor designed by using Zr-based metal–organic frameworks (Zr-MOFs) for the detection of GBM-derived exosomes with practical application. In the design, a peptide ligand can specifically bind with human epidermal growth factor receptor (EGFR) and EGFR variant (v) III mutation (EGFRvIII), which are overexpressed on the GBM-derived exosomes. Meanwhile, Zr-MOFs encapsulated with methylene blue can absorb on the surface of the exosomes due to the interaction between Zr4+ and the intrinsic phosphate groups outside of exosomes. Consequently, the concentration of exosomes can be directly quantified by monitoring the electroactive molecules inside MOFs, ranging from 9.5 × 103 to 1.9 × 107 particles/μL with the detection of limit of 7.83 × 103 particles/μL. Furthermore, this proposed biosensor can distinguish GBM patients from healthy groups, demonstrating the great prospect for early clinical diagnosis.

Immunoassay-aptasensor for the determination of tumor-derived exosomes based on the combination of magnetic nanoparticles and hybridization chain reaction

“…11 At present, the recognized standard methods widely used for exosome quan-tication and analysis include transmission electron microscopy (TEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), atomic force microscopy (AFM), western blot (WB), enzyme-linked immunosorbent assay (ELISA), tunable resistive pulse sensing (RPS), ow cytometry and mass spectrometry (MS). [11][12][13][14] All of the aforementioned methods are used to analyze one characteristic aspect of exosomes, e.g. TEM is usually used to characterize the morphological characteristics, DLS and NTA are used to analyse the size and concentration of exosomes.…”

“…Recently, considering the importance of exosomes in the liquid biopsy of cancer, many studies have explored new detection techniques over the past few decades. 16 A series of novel technologies have been developed for the determination of exosomes, including uorescence detection, 17 electrochemical biosensors, 5,14,18,19 immunosensors, 13,20 surface plasmon resonance (SPR), [21][22][23] microuidic devices, 21 electrochemiluminescence, 24 aptasensors, 25 and spectroscopic analysis. 26 However, these established exosome assays usually involve labour-intensive steps and require extended quantitative protocols and expensive laboratory infrastructures.…”

Role of Tumor-Derived Extracellular Vesicles in Glioblastoma

“…The ability of EVs to cross the blood-brain barrier (BBB) is an important factor in considering their success in delivering drugs to TME. GBM-derived specific EVs can cross the BBB and circulate in body fluids, so they can be used as non-invasive biomarkers for early diagnosis of GBM [123,124]. GBM-derived EVs could enhance BBB permeability [125].…”

Recent Progress on the Isolation and Detection Methods of Exosomes

“…The schematic diagram of detection is shown in Figure 5. In addition, some analytical methods [44,60] used other protein aptamers to detect exosomes. At the same time, based on the labeling of surface proteins of exosomes in serum with seven fluorescent aptamers, Sun et.…”