Inhaled nanoparticles develop a complex protein corona: biological importance and implications for sustained release formulations

Abhinav Kumar, Elif Melis Bicer, Paul Pfeffer, Marco Monopoli, Kenneth Dawson, Anders Blomberg, Annelie Behndig, Lea Ann Dailey, Ben Forbes, Ian Mudway

Nanoparticle delivery systems are being designed as carriers for targeting drugs to the lungs, but when they deposit into lung lining fluid they are surface-modified by interaction with proteins and lipids.  To date there is little information on the biomolecular corona that forms around nanoparticles in the lungs.  Here we identify the protein corona that forms rapidly around nanoparticles in human lung lining fluid.  Nanoparticles (silicon dioxide and polyvinyl acetate) were incubated for 1 h in human lung lining fluid and the hard corona was isolated.  The proteins adhered to the particle surface were extracted and run through a 1-D SDS-gel.  The bands of interest were cut and the proteins were extracted using trypsin digestion prior to injecting into the LC-MS/MS.  Comparison with the Uniprot-SwissProt Human proteome database revealed enrichment around the particle surface of surfactant proteins, complement factors, immunoglobulins and other proteins with profound immunological actions, such as complement components.  Surfactant proteins act as innate immunity proteins and opsonise microbes and particles and promote their clearance by phagocytosis by alveolar macrophages.  Surfactant protein A coating has been shown to enhance the uptake of metal oxide nanoparticles as compared to metal oxide nanoparticles coated with albumin (the major plasma protein).  This data improves our understanding of the behaviour of inhaled nanoparticles and informs the design of safe and effective nanomedicines such as those that aim to control the release of drugs in the lungs.


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