LIPOSOME PROTEIN CORONA IN VIVO: FROM FUNDAMENTAL PRINCIPLES TO A TOOL FOR CANCER BIOMARKER DISCOVERY

Abstract

Nanoparticles (NPs) are instantly modified once injected in the bloodstream because of their surface interaction with blood components. The spontaneous coating of NPs by proteins, once in contact with biological fluids, has been termed the ‘protein corona’. This surface biotransformation of nanomaterials has been postulated as a modulatory factor for their overall pharmacological, toxicological and therapeutic profile. In this thesis, we developed a robust protocol to comprehensively characterize the previously elusive in vivo protein corona onto intravenously administered clinically established liposomal NPs, recovered from the blood circulation of rodents and humans. Our data suggest that the molecular complexity of the in vivo protein corona cannot be adequately predicted by the in vitro plasma incubations of NPs. Further examination of the dynamics of liposome-protein interactions in vivo revealed that protein corona is a dynamic entity that evolves with time. In addition, we offer the previously unreported molecular description of the in vivo human protein corona adsorbed onto PEGylated liposomal vesicles (Caelyx®), intravenously infused and subsequently recovered from recurrent ovarian carcinoma patients. Lastly, we provide initial evidence of the potential exploitation of the in vivo protein corona as a novel scavenging tool to comprehensively analyse the blood circulation proteome and to facilitate the discovery of new biomarker molecules for cancer diagnostics. In summary, this work not only provides a thorough characterization of the in vivo protein corona but also provides proof-of concept of the clinical exploitation of protein corona fingerprinting as a tool for body-fluid based biomarker discovery.

Date of Award	31 Dec 2017
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Kostas Kostarelos (Supervisor), Mariarosa Mazza (Supervisor) & Zahraa Al-Ahmadyv (Supervisor)