The goal of the biomarker field is to develop simple non-invasive tests that allow early disease detection and monitor disease progression. Blood is the most studied biomarker source because of its dynamic composition that reflects the pathological state. Proteins are the most common type of biomarkers, used in medical diagnostics so far. One of the major obstacles to identify protein biomarkers is the highly dynamic concentration range of plasma proteome (more than 10 orders of magnitude) which exceeds the current capability of proteomic analysis and therefore limits the identification of low abundance protein candidates. In this study, we propose the use of clinically used nanoparticles (liposomes) as a platform to scavenge the blood pool for biomarkers. Intravenously injected nanoparticles are instantly covered by a complex mixture of blood proteins, referred to as ‘protein corona’. In our recent reports, we described for the first time a protocol to recover protein-coated liposomes from the blood circulation of mice, purify the unbound proteins and quantitatively and qualitatively characterize the protein corona. A striking observation was that the most abundant proteins of liposomal corona were not the most abundant plasma proteins [1,2]. We will report for the first time our results from a clinical trial in collaboration Manchester Cancer Research Centre to thoroughly characterise the formation of in vivo protein corona in ovarian cancer patients injected with PEGylated, doxorubicin-encapsulated liposomes. Our results demonstrate, that liposomes are able capture low molecular weight, low abundant plasma proteins. The elimination of background, high abundant proteins enabled the uncovering of multiple tumor-associated proteins that could not be directly detected by plasma analysis. [1] M. Hadjidemetriou, Z. Al-Ahmady, M. Mazza, R. F. Collins, K. Dawson, K. Kostarelos. In vivo biomolecule corona around blood-circulating, clinically-used and antibody-targeted lipid bilayer nanoscale vesicles ACS Nano, 2015, 9, 8142. [2] M. Hadjidemetriou, Z. Al-Ahmady, K. Kostarelos. Time-evolution of in vivo protein corona onto blood-circulating PEGylated liposomal doxorubicin (DOXIL) nanoparticles. Nanoscale 2016, 8, 6948-57.

Human in vivo nanoparticle protein corona in ovarian carcinoma patients: A novel tool for biomarker discovery

253rd National Meeting (2017)

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