Target, Treat, and Track: Superparamagnetic Iron Oxide Nanoparticles (SPION) Driven Theranostic Delivery of Antimicrobials to the Lungs

Gabriela Wyszogrodzka-Gaweł,1 Maciej Stróżyk,1 Marta Skoda,1 Magdalena Osial,2 Ewelina Baran,3 Aleksander Mendyk1 1Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; 2Institute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland; 3Institute of Technology, University of the National Education Commission, Kraków, PolandCorrespondence: Gabriela Wyszogrodzka-Gaweł, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland, Email [email protected]: This review explores the emerging potential of theranostic approaches in the pulmonary delivery of antimicrobial agents, with particular attention to recent FDA warnings concerning inhaled antifungal therapies. Pulmonary infections remain difficult to treat effectively due to the limitations of systemic drug delivery, anatomical and physiological barriers within the lungs, and microbial strategies that promote colonization. Inhaled drug delivery offers a targeted alternative but faces significant challenges, including the inherent variability of lung anatomy, disease-induced pulmonary alterations, and host defence mechanisms. We examine the crucial role of lung imaging in enabling theranostic applications, emphasizing magnetic resonance imaging (MRI) as the most promising modality due to its ability to provide non-invasive, radiation-free, and repeatable assessments of drug deposition. Within this context, the use of superparamagnetic iron oxide nanoparticles (SPIONs) as MRI contrast agents is critically assessed. SPIONs offer a safer alternative to gadolinium-based agents and hold considerable promise for improving the precision of imaging and treatment monitoring in the lungs. The article also outlines the significant regulatory barriers to the development and clinical adoption of inhaled antimicrobial therapies. These include the lack of standardized patient selection criteria, poorly defined clinical endpoints, and the inherent complexity of trial design for heterogeneous patient populations. To address these issues, we propose a conceptual framework for translating inhaled theranostic formulations into personalized antimicrobial therapies. This includes individualized dose adjustments based on imaging data and real-time monitoring of drug concentrations at the infection site. Such a tailored approach could significantly enhance treatment outcomes and meet the urgent clinical need for safer, more effective inhaled antimicrobial treatments. Keywords: theranostic, pulmonary delivery, inhaled antibiotics, inhaled antifungals, SPIONs, MRI