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人唾液衍生外泌体的定量纳米结构和单分子力谱生物分子分析。

Quantitative nanostructural and single-molecule force spectroscopy biomolecular analysis of human-saliva-derived exosomes.

机构信息

Department of Chemistry and Biochemistry and California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.

出版信息

Langmuir. 2011 Dec 6;27(23):14394-400. doi: 10.1021/la2038763. Epub 2011 Nov 9.

DOI:10.1021/la2038763
PMID:22017459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3235036/
Abstract

Exosomes are naturally occurring nanoparticles with unique structure, surface biochemistry, and mechanical characteristics. These distinct nanometer-sized bioparticles are secreted from the surfaces of oral epithelial cells into saliva and are of interest as oral-cancer biomarkers. We use high- resolution AFM to show single-vesicle quantitative differences between exosomes derived from normal and oral cancer patient's saliva. Compared to normal exosomes (circular, 67.4 ± 2.9 nm), our findings indicate that cancer exosome populations are significantly increased in saliva and display irregular morphologies, increased vesicle size (98.3 ± 4.6 nm), and higher intervesicular aggregation. At the single-vesicle level, cancer exosomes exhibit significantly (P < 0.05) increased CD63 surface densities. To our knowledge, it represents the first report detecting single-exosome surface protein variations. Additionally, high-resolution AFM imaging of cancer saliva samples revealed discrete multivesicular bodies with intraluminal exosomes enclosed. We discuss the use of quantitative, nanoscale ultrastructural and surface biomolecular analysis of saliva exosomes at single-vesicle- and single-protein-level sensitivities as a potentially new oral cancer diagnostic.

摘要

外泌体是具有独特结构、表面生物化学和机械特性的天然存在的纳米颗粒。这些独特的纳米级生物颗粒从口腔上皮细胞表面分泌到唾液中,作为口腔癌生物标志物很有研究价值。我们使用高分辨率原子力显微镜 (AFM) 显示来自正常和口腔癌患者唾液的外泌体之间的单囊泡定量差异。与正常外泌体(圆形,67.4 ± 2.9nm)相比,我们的研究结果表明,癌症外泌体群体在唾液中的明显增加,表现出不规则的形态、增加的囊泡大小(98.3 ± 4.6nm)和更高的囊泡间聚集。在单囊泡水平上,癌症外泌体表现出明显(P < 0.05)增加的 CD63 表面密度。据我们所知,这代表了首次检测到单外泌体表面蛋白变化的报道。此外,对癌症唾液样本的高分辨率 AFM 成像显示了具有腔内外泌体的离散多泡体。我们讨论了使用定量、纳米级超微结构和表面生物分子分析唾液外泌体在单囊泡和单蛋白水平的敏感性,作为一种潜在的新型口腔癌诊断方法。

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