Abstract The development and implementation of biomarker-based screening tools for ovarian cancer require novel analytical platforms to enable the discovery of biomarker panels that will overcome the limitations associated with the clinically used CA-125.The systematic discovery of protein biomarkers directly from human plasma using proteomics remains extremely challenging, due to the wide concentration range of plasma proteins. Here, we describe the use of lipid-based nanoparticles (NPs) as an ‘omics’ enrichment tool to amplify cancer signals in the blood and to uncover disease specific signatures. We aimed to exploit the spontaneous interaction of clinically-used liposomes (Caelyx®) with plasma proteins, also known as’ protein corona’ formation, in order to facilitate the discovery of previously unreported differentially abundant molecules. Caelyx® liposomes were incubated with plasma samples obtained from advanced ovarian carcinoma patients and healthy donors and corona-coated liposomes were subsequently recovered. Comprehensive comparison between ‘healthy’ and ‘diseased’ corona samples by label-free proteomics resulted in the identification of multiple differentially abundant proteins. Moreover, immunoassay-based validation of selected proteins demonstrated the potential of nanoparticle-platform proposed to discover novel molecules with great diagnostic potential. This study proposes a nanoparticle-enabled workflow for plasma proteomic analysis in healthy and diseased states and paves the way for further work needed to discover and validate panels of novel biomarkers for disease diagnosis and monitoring.

中文翻译：

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用于卵巢癌血液生物标志物发现的纳米清除剂

摘要 基于生物标志物的卵巢癌筛查工具的开发和实施需要新的分析平台来发现生物标志物组合，以克服与临床使用的 CA-125 相关的局限性。由于血浆蛋白的浓度范围很广，蛋白质组学仍然极具挑战性。在这里，我们描述了使用基于脂质的纳米粒子 (NPs) 作为“组学”富集工具来放大血液中的癌症信号并揭示疾病特异性特征。我们旨在利用临床使用的脂质体 (Caelyx®) 与血浆蛋白的自发相互作用，也称为“蛋白冠”形成，以促进发现以前未报告的差异丰富的分子。Caelyx® 脂质体与从晚期卵巢癌患者和健康供体获得的血浆样品一起孵育，随后回收了电晕包被的脂质体。通过无标记蛋白质组学对“健康”和“患病”电晕样本进行综合比较，可以识别出多种差异丰富的蛋白质。此外，对选定蛋白质的基于免疫测定的验证证明了纳米颗粒平台在发现具有巨大诊断潜力的新分子方面的潜力。这项研究提出了一种支持纳米粒子的工作流程，用于健康和患病状态下的血浆蛋白质组学分析，并为发现和验证用于疾病诊断和监测的新型生物标志物组所需的进一步工作铺平了道路。