Exosomes: A potential tool for immunotherapy of ovarian cancer

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 18, 2023

Ovarian cancer is a malignant tumor of the female reproductive system, with very poor prognosis and high mortality rates. Chemotherapy radiotherapy are most common treatments for ovarian cancer, unsatisfactory results. Exosomes subpopulation extracellular vesicles, which have diameter approximately 30–100 nm secreted by many different types cells in various body fluids. highly stable effective carriers immunotherapeutic drugs. Recent studies shown that exosomes involved cellular responses microenvironment, influencing development therapeutic efficacy exhibiting dual roles inhibiting promoting development. also contain variety genes related to immunotherapy could be potential biomarkers diagnosis prognosis. Undoubtedly, great field immunotherapy. However, translation this idea clinic has not occurred. Therefore, it important understand how used regulate progression. In review, we summarize fluids mechanisms influence response. We discuss prospects clinical application exosome-based cancer.

Language: Английский

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Microfluidic Impedance Cytometry Enabled One‐Step Sample Preparation for Efficient Single‐Cell Mass Spectrometry

Small, Journal Year: 2024, Volume and Issue: 20(26)

Published: March 14, 2024

Abstract Single‐cell mass spectrometry (MS) is significant in biochemical analysis and holds great potential biomedical applications. Efficient sample preparation like sorting (i.e., separating target cells from the mixed population) desalting moving off non‐volatile salt solution) urgently required single‐cell MS. However, traditional methods suffer complicated operation with various apparatus, or insufficient performance. Herein, a one‐step strategy by leveraging label‐free impedance flow cytometry (IFC) based microfluidics proposed. Specifically, IFC framework to characterize sort single‐cells adopted. Simultaneously sorting, cell transferred local high‐salinity buffer MS‐compatible solution. In this way, are achieved collected can be directly fed for MS analysis. A high efficiency (>99%), cancer purity (≈87%), whole workflow of impedance‐based separation normal (MCF‐10A) (MDA‐MB‐468) verified. As standalone module, microfluidic chip compatible variety methods, envisioned provide new paradigm efficient preparation, further multi‐modal electrical metabolic) characterization single‐cells.

Language: Английский

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Intact living-cell electrolaunching ionization mass spectrometry for single-cell metabolomics

Chemical Science, Journal Year: 2022, Volume and Issue: 13(27), P. 8065 - 8073

Published: Jan. 1, 2022

While single-cell mass spectrometry can reveal cellular heterogeneity and the molecular mechanisms of intracellular biochemical reactions, its application is limited by insufficient detection sensitivity resulting from matrix interference sample dilution. Herein, we propose an intact living-cell electrolaunching ionization (ILCEI-MS) method. A capillary emitter with a narrow-bore, constant-inner-diameter ensures that entire living cell enters MS ion-transfer tube. Inlet improves utilization, no solvent required, preventing dilution interference. Based on these features, greatly improved, average signal-to-noise (S/N) ratio about 20 : 1 peaks in TIC ILCEI-MS. high throughput 51 cells per min was achieved ILCEI-MS for metabolic profiling multiple lines, 368 metabolites were identified. Further, more than 4000 primary single digested fresh multi-organ tissues mice detected ILCEI-MS, demonstrating applicability reliability.

Language: Английский

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Single-Cell Unsaturated Lipid Profiling for Studying Chemoresistance Heterogeneity of Triple-Negative Breast Cancer Cells

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 9, 2024

Chemoresistance to triple-negative breast cancer (TNBC) is a critical issue in clinical practice. Lipid metabolism takes unique role cells; especially, unsaturated lipids involving cell membrane fluidity and peroxidation are highly remarked. At present, for the lack of high-resolution molecular recognition platform at single-cell level, it still hard systematically study chemoresistance heterogeneity based on lipid unsaturation proportion. By designing mass spectrometry workflow CyESI-MS, we profiled TNBC cells evaluate lipidomic remodeling under platinum stress. Profiling revealed polyunsaturated proportion cisplatin treatment. A cluster identified by accumulation was found be involved sensitivity. Furthermore, that could regulated fatty acid supplementation, which determinates composition lipids. These discoveries provide insights monitoring controlling cellular proportions overcome cancer.

Language: Английский

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Spatiotemporal metabolomic approaches to the cancer-immunity panorama: a methodological perspective

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 18, 2024

Language: Английский

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In-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 23, 2024

Abstract Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. However, metabolomics remains challenging because of limited metabolite coverage inability to discriminate isomers. Herein, we establish a platform in-depth organic mass cytometry. Extended analysis time guarantees sufficient MS/MS acquisition identification isomers discrimination while online sampling ensures high-throughput method. The largest number identified metabolites (approximately 600) are achieved in single cells fine subtyping MCF-7 first demonstrated by an investigation on differential levels 3-hydroxybutanoic acid among clusters. Single-cell transcriptome reveals differences expression downstream antioxidative stress genes, such as metallothionein 2 (MT2A), fluorescence-activated cell sorting assay confirms positive relationship between target proteins; these results suggest that provides cancer with different ability resist surrounding oxidative stress. Our method paves way deep metabolome investigations physiological pathological processes occur during cancer.

Language: Английский

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Efficient Sample Preparation System for Multi-Omics Analysis via Single Cell Mass Spectrometry

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(18), P. 7212 - 7219

Published: April 20, 2023

Mass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging the manipulation cells lack in-fly cellular digestion extraction approaches. Here, we present streamlined strategy highly automatic single-cell by MS. We developed 10-pL-level microwell chip housing individual whose proteins were found to be digested 5 min, which 144 times shorter than traditional bulk digestion. Besides, an automated picoliter system was sampling metabolites, phospholipids, tandem from same cell. Also, 2 min MS2 spectra obtained 700 pL solution cell sample. In addition, 1391 proteins, metabolites detected one within 10 min. further analyzed cancer tissue samples, achieving up 40% increase classification accuracy using comparison with single-omics analysis. This MS analyzing information investigation heterogeneity phenotyping biomedical applications.

Language: Английский

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Single-Cell Metabolomics-Based Strategy for Studying the Mechanisms of Drug Action

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(10), P. 4712 - 4720

Published: March 1, 2023

Studying the mechanisms of drug antitumor activity at single-cell level can provide information about responses cell subpopulations to therapy, which is essential for accurate treatment cancer. Due small size single cells and low contents metabolites, metabolomics-based approaches studying action are lacking. Herein, we develop a label-free platform based on metabolomics (sMDA-scM) by integrating intact living-cell electro-launching ionization mass spectrometry (ILCEI-MS) with analysis. Using this platform, reveal that non-small-cell lung cancer (NSCLC) treated gefitinib be clustered into two different metabolic responses. The glutathione pathway subpopulation containing 14.4% not significantly affected gefitinib, exhibiting certain resistance characteristics. presence these masked judgment whether cysteine methionine was remarkably influenced in analysis overall average results, revealing heterogeneity response NSCLC treatment. findings basis evaluating early therapeutic effects clinical medicines insights overcoming subpopulations.

Language: Английский

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One-Shot Single-Cell Proteome and Metabolome Analysis Strategy for the Same Single Cell

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(14), P. 5499 - 5508

Published: March 28, 2024

Characterizing the profiles of proteome and metabolome at single-cell level is great significance in multiomic studies. Herein, we proposed a novel strategy called one-shot analysis (scPMA) to acquire information individual one injection LC-MS/MS analysis. Based on scPMA strategy, total workflow was developed achieve capture, nanoliter-scale sample pretreatment, LC separation enzyme-digested peptides metabolites, dual-zone MS/MS detection for profiling. Benefiting from realized dual-omic single tumor cells, including A549, HeLa, HepG2 cells with 816, 578, 293 protein groups 72, 91, 148 metabolites quantified average. A perspective experiment investigating doxorubicin-induced antitumor effects both aspects also performed.

Language: Английский

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Methods developments of mass spectrometry based single cell metabolomics

TrAC Trends in Analytical Chemistry, Journal Year: 2023, Volume and Issue: 164, P. 117086 - 117086

Published: May 15, 2023

Language: Английский

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