A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona
A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona
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DOI：
10.1016/j.biomaterials.2018.10.011
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发表时间：
2019-01-01
期刊：
影响因子：
14
通讯作者：
Kostarelos, Kostas
中科院分区：
文献类型：
--
作者：
Hadjidemetriou, Marilena;Al-ahmady, Zahraa;Kostarelos, Kostas
对血浆生物标志物发现的重大投资与目前临床使用的生物标志物数量非常少之间的显著差异强调了对发现技术的需求。通过蛋白质组学发现存在于人类血液中的蛋白质生物标志物是非常具有挑战性的，这是由于血液蛋白质的动态浓度范围很大。在这里，我们描述了使用血液循环脂质为基础的纳米粒子（NPs）作为清除工具，全面分析血液蛋白质组。我们的目的是利用一旦注射到血流中，NP与血浆蛋白的自发相互作用，称为“蛋白质冠”，以促进肿瘤特异性分子的捕获。我们采用了两种不同的肿瘤模型，皮下黑色素瘤模型（B16-F10）和人肺癌异种移植模型（A549），并通过质谱法全面比较了在健康和荷瘤小鼠中静脉内给药的临床使用的脂质体上形成的体内蛋白质冠。所获得的结果表明，血液循环脂质体表面捕获并扩增了广泛的不同蛋白质，包括低分子量（MW）和低丰度肿瘤特异性蛋白质（组织渗漏的细胞内产物），这些蛋白质不能通过血浆分析检测到，进行比较。最引人注目的是，发现在异种移植模型中形成的NP（脂质体）冠由鼠宿主反应蛋白以及从接种和生长的人癌细胞释放的人蛋白组成。这项研究提供了直接的证据，体内NP蛋白冠可以被认为是一个有价值的工具，以丰富血液蛋白质组学分析，并允许在实验疾病模型中发现潜在的生物标志物。
The prominent discrepancy between the significant investment towards plasma biomarker discovery and the very low number of biomarkers currently in clinical use stresses the need for discovery technologies. The discovery of protein biomarkers present in human blood by proteomics is tremendously challenging, owing to the large dynamic concentration range of blood proteins. Here, we describe the use of blood-circulating lipid-based nanoparticles (NPs) as a scavenging tool to comprehensively analyse the blood proteome. We aimed to exploit the spontaneous interaction of NPs with plasma proteins once injected in the bloodstream, known as 'protein corona', in order to facilitate the capture of tumor-specific molecules. We employed two different tumor models, a subcutaneous melanoma model (B16-F10) and human lung carcinoma xenograft model (A549) and comprehensively compared by mass spectrometry the in vivo protein coronas formed onto clinically used liposomes, intravenously administered in healthy and tumor-bearing mice. The results obtained demonstrated that blood circulating liposomes surface-capture and amplify a wide range of different proteins including low molecular weight (MW) and low abundant tumor specific proteins (intracellular products of tissue leakage) that could not be detected by plasma analysis, performed in comparison. Most strikingly, the NP (liposomal) corona formed in the xenograft model was found to consist of murine host response proteins, as well as human proteins released from the inoculated and growing human cancer cells. This study offers direct evidence that the in vivo NP protein corona could be deemed as a valuable tool to enrich the blood proteomic analysis and to allow the discovery of potential biomarkers in experimental disease models.