Investigation of Urinary Exosome Metabolic Patterns in Membranous Nephropathy by Titania‐Assisted Intact Exosome Mass Spectrometry

Abstract

Exosomes are regarded as the emerging potential targets for liquid biopsy and bioprocess study owing to their abundant inclusive cargos that carry significant disease information. In addition, metabolites have been promising biomarkers for diagnosis. However, little metabolic research on exosomes is carried out by now. Herein, the mix‐crystal titania‐assisted laser desorption/ionization mass spectrometry (LDI‐MS) method is established, which features fast speed, high throughput, and efficiency, to directly extract urinary exosome metabolic patterns of healthy controls (HC) and membrane nephropathy (MN) patients. Besides, this method is also adopted to acquire the primitive urinary metabolic patterns from the same samples for comparison. By taking advantage of principal component analysis, unpaired parametric t‐test, and orthogonal partial least squares discriminant analysis on the exosome metabolic patterns, 27 significant m/z signals are filtrated, which possess more prominent differentiation capacity toward HC and MN patients (AUC = 0.942), and hold greater potential in MN diagnosis, compared to primitive urine (AUC = 0.801). The work reveals the important clinical value of exosome metabolic analysis, and paves a way to exosome‐based diagnosis at metabolomic level toward large‐scale clinical use.

Exosome Metabolic Patterns on Aptamer-Coupled Polymorphic Carbon for Precise Detection of Early Gastric Cancer

“…The results suggest that exosome metabolic patterns from different sources are sufficiently heterogenetic for disease discrimination, with the same effectiveness as their original cells, and CoMPC@Au-Apt can successfully decipher exosome metabolic patterns. It is worth mentioning that this study designed a material with nanostructures that can not only act as an adsorbent for exosome capture but also serve as an LDI-MS matrix for high-throughput exosomal metabolic analysis, which is different from the previous research . Moreover, as reported, tumor cells only exist in peripheral blood with extremely low abundance; therefore, exosome metabolic patterns are more available for noninvasive diagnosis.…”

“…It is worth mentioning that this study designed a material with nanostructures that can not only act as an adsorbent for exosome capture but also serve as an LDI-MS matrix for high-throughput exosomal metabolic analysis, which is different from the previous research. 20 Moreover, as reported, tumor cells only exist in peripheral blood with extremely low abundance; 37 therefore, exosome metabolic patterns are more available for noninvasive diagnosis.…”

“…However, ultracentrifugation or co-precipitation separation are high-cost and time-consuming . More seriously, traditional matrices are accompanied by severe background interference in the low-mass range because of self-dissociation, restricting the application of LDI-MS in metabolic analysis . With the deepening research of nanoscience, materials with nanostructures can be substitutes. − Thereinto, carbon nanomaterials got much attention owing to good UV absorption and electronic conductivity .…”

In Vitro Diagnostic Examination and Prognosis Surveillance by Hierarchical Heterojunction-Assisted Metabolic Analysis

“…Conventional organic matrices including α-cyano-4hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) prefer to produce interference signals in the low mass range, leading to huge difficulty in metabolite detection. 6 The introduction of nanomaterials with good ultraviolet absorption capacity well avoids the background interference 7−12 component singleness may be the ringleader leading to the unsatisfactory separation of electron−hole pairs on the interface of the matrix. 13 As is well known, the matrix interface is the location that realizes generation, separation, transfer, and recombination of electron−hole pairs, while the recombination rate on the unitary interface is normally faster than trapping and transfer rates.…”

“…Laser desorption/ionization mass spectrometry (LDI-MS) stands out for high throughput, analysis speed within seconds, simple sample preparation, and sample consumption at the micro/nanoliter level, thereby being the hot research topic in metabolic analysis-based precise medicine. , Nevertheless, LDI-MS performance relies on the matrix. Conventional organic matrices including α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) prefer to produce interference signals in the low mass range, leading to huge difficulty in metabolite detection . The introduction of nanomaterials with good ultraviolet absorption capacity well avoids the background interference − but only provides inadequate ionization efficiency for low-abundance metabolites, which is far away from clinical application.…”