RT Journal Article T1 Delayed alveolar clearance of nanoparticles through control of coating composition and interaction with lung surfactant protein A A1 Carregal Romero, Susana A1 Groult, Hugo A1 Cañadas Benito, Olga A1 A-Gonzalez, Noelia A1 Lechuga Vieco, Ana Victoria A1 García Fojeda, Belén A1 Herranz, Fernando A1 Pellico, Juan A1 Hidalgo, Andrés A1 Casals, Cristina A1 Ruiz Cabello, Jesús AB The coating composition of nanomedicines is one of the main features in determining the medicines' fate, clearance, and immunoresponse in the body. To highlight the coatings' impact in pulmonary administration, two micellar superparamagnetic iron oxide nanoparticles (SPION) were compared. These nanoparticles are similar in size and charge but have different coatings: either phosphatidylcholine (PC-SPION) or bovine serum albumin (BSA-SPION). The aim of the study was to increase the understanding of the nano-bio interaction with the cellular and non-cellular components of the lung and underline valuable coatings either for local lung-targeted drug delivery in theranostic application or patient-friendly route systemic administration. PC-SPION and BSA-SPION were deposited in the alveoli by in vivo instillation and, despite the complexity of imaging the lung, SPION were macroscopically visualized by MRI. Impressively, PC-SPION were retained within the lungs for at least a week, while BSA-SPION were cleared more rapidly. The different lung residence times were confirmed by histological analysis and supported by a flow cytometry analysis of the SPION interactions with different myeloid cell populations. To further comprehend the way in which these nanoformulations interact with lung components at the molecular level, we used fluorescence spectroscopy, turbidity measurements, and dynamic light scattering to evaluate the interactions of the two SPION with surfactant protein A (SP-A), a key protein in setting up the nanoparticle behavior in the alveolar fluid. We found that SP-A induced aggregation of PC-SPION, but not BSA-SPION, which likely caused PC-SPION retention in the lung without inducing inflammation. In conclusion, the two SPION show different outcomes from interaction with SP-A leading to distinctive fate in the lung. PC-SPION hold great promise as imaging and theranostic agents when prolonged pulmonary drug delivery is required. PB Elsevier SN 0928-4931 YR 2021 FD 2021-11-14 LK https://hdl.handle.net/20.500.14352/4680 UL https://hdl.handle.net/20.500.14352/4680 LA eng NO CRUE-CSIC (Acuerdos Transformativos 2021) NO Ministerio de Ciencia e Innovación (MICINN) NO Gobierno Vasco.ELKARTEK Program NO BBVA Foundation DS Docta Complutense RD 7 may 2024