The biomolecule corona mediates pulmonary delivery of nanomedicine.

Pulmonary delivery of therapeutics (e.g., biologics, antibiotics, and chemotherapies) encapsulated in nanoparticles is desirable for the ability to provide a localised treatment, bypassing the harsh gastrointestinal environment. However, limited understanding of the biological fate of nanoparticles upon administration to the lungs hinders translation of pre-clinical investigations into viable therapies. A key knowledge gap is the impact of the pulmonary biomolecular corona on the functionality of nanoparticles. In this review, opportunities and challenges associated with pulmonary nanoparticle delivery are elucidated, highlighting the impact of the pulmonary biomolecular corona on immune recognition and nanoparticle internalisation in target cells. Recent investigations detailing the influence of proteins, lipids and mucin derived from pulmonary surfactants on nanoparticle behaviour are detailed. In addition, latest approaches in modulating plasma protein corona upon systemic delivery for biodistribution to the lungs are also discussed. Key examples of reengineering nanoparticle structure to mediate formation of biomolecule corona are provided. This review aims to provide a comprehensive understanding on biomolecular corona of nanoparticles for pulmonary delivery, while accentuating their significance for successful translation of newly investigated therapeutics.