Engineering of pulmonary surfactant corona on inhaled nanoparticles to operate in the lung system

Exposure of inhaled nanoparticles (NPs) to the deep lung tissue results in the adsorption of pulmonary surfactant (PSf) on the surface of NPs and the formation of a biomolecular corona. The adsorption of the peculiar phospholipids (PLs) and surfactant proteins (SPs) provides NPs with a new bio-identity, which likely changes their corresponding interactions with cells and other bio-systems. Exploring the interaction of NPs with the PSf film at the alveolar air-fluid interface can provide valuable insights into the role of biofluids in the cellular uptake of NPs and their nanotoxic effects. Wrapping biomembranes around NPs and the formation of lipoprotein corona regulate viscoelastic changes, NP insertion into the membrane, and cellular uptake of NPs. In this review, a concise overview has been presented on the engineering of PSf on inhaled NPs to operate in lung environment. First, the physiological barriers in the pulmonary delivery of NPs and approaches to regulating their pulmonary fate are introduced and rationalized. Next, a short description is given on the different sources used for exploring the interfacial performance of inhaled NPs in vitro. A discussion is then presented on SP corona formation on the surface of inhaled NPs, coronal proteome/lipidome in respiratory tract lining fluid (RTLF), regulation of NP aggregation and surfactant flow characteristics, PSf corona and its functional role in the cellular uptake of NPs, followed by explanations on the clinical correlations of PSf corona formation/inhibition on the surface of NPs. Finally, the challenges and future perspectives of the field have been discussed. This review can be harnessed to exploit PSf for the development of safe and bio-inspired pulmonary drug delivery strategies.