Infection-Phase Biomolecular Coronas in Inhaled Nanomedicine.

An inhaled nanomedicine encounters two successive forms of remodeling: device-related changes during aerosol generation and biological conditioning after deposition. Respiratory infection adds a moving interface, as epithelial secretion, surfactant composition, plasma leakage, and neutrophil-derived material vary across airway compartments and over time. Pulmonary and disease-corona studies already establish that host environments influence nanoparticle identity. The next question is how this knowledge should change formulation selection and dosing for infected lungs. We propose an infection-phase framework based on measured, overlapping airway environments. It connects the post-aerosol particle to its surface-associated biomolecules, distinguishes this interface from aggregation and bulk mucus effects, and links analytical measurements to functional delivery. A staged research program begins with one compartment and two contrasting environments, then adds controlled particle-transfer experiments, candidate-component perturbation, and donor-level validation. Lipid nanoparticles, polymeric carriers, and nanozymes require different functional endpoints within this shared framework. The immediate translational output is a biorelevant performance stress test that identifies robust or environment-selective formulations and guides the next experiment.