What are the biological and therapeutic implications of biomolecule corona formation on the surface of inhaled nanomedicines?

Abstract

Respiratory tract lining fluid is not blood It may be a statement of the obvious, but one would not expect the corona formed on a nanoparticle surface following deposition in the lungs to resemble that surrounding nanoparticles after exposure to plasma or whole blood, or for that matter cell culture medium. This is self-evident; the only problem is, no one has quite shown it yet. Respiratory tract lining fluid (RTLF) is compositionally very different from blood plasma; varying in ionic strength, antioxidant, lipid and protein content. RTLF composition also varies markedly throughout the length of the respiratory tract, reflecting local contributions from mucus-secreting cells in the major conducting airways and surfactant from type II pnuemoctyes in the alveolar region. While the RTLF does contain a wide variety of plasma-derived proteins including albumin, transferrin, apolipoprotein A-1, haptoglobin, α-1-antitrypsin and α-2-macroglobulin [1]; its proteome is also rich in lung-specific proteins, such as Clara cell secretory protein 16 and pulmonary surfactant proteins A and D, which play important roles in innate host defense [2]. In addition, in the alveolar region, surfactant proteins B and C help to stabilize the monolayer of phospholipids (primarily phosphatidylcholine, phosphatidylglycerol) and cholesterol, which lowers the surface tension and prevents alveolar collapse during expiration [3]. It follows that the corona formed on the surface of an inhaled particle incident at the air–lung interface will reflect the local composition of the RTLF, and comprise a variety of different bio molecules such as phospholipids in addition to proteins. It is thus more accurate to speak of a ‘bio molecule’ corona rather than a ‘protein’ corona in this case. In collaboration with several other groups, we have recently begun to characterize the biomolecule corona formed on the surface of silica nanoparticles when incubated within concentrated bronchoalveolar lavage fluid samples obtained from healthy humans and patient groups with various lung diseases. For this initial characterization, silica nanoparticles were chosen as a model particle system because their protein corona formation has been studied extensively in human plasma and fetal bovine serum. Mass spectrometry was used to characterize the protein component of the biomolecule corona, identifying over 400 distinct proteins on the particle surface following incubation in RTLF from healthy young adults [4]. In contrast, a significantly lower number of proteins adsorbed to silica nanoparticles incubated in human plasma, ranging from approximately 63 to 166 distinct proteins in different studWhat are the biological and therapeutic implications of biomolecule corona formation on the surface of inhaled nanomedicines?