Assessment of pulmonary mucociliary transport using magnetic nanoparticles: influence of their surface potential

Inhaled aerocontaminants are removed from the lungs by pulmonary mucociliary transport (MCT) as an important defense mechanism. This study was undertaken to investigate the influence of the surface potential of magnetic nanoparticles (MNPs) on the MCT in murine lungs by use of magnetic particle imaging (MPI). Three kinds of MNPs (carboxymethyl dextran magnetite (CM), alkali-treated dextran magnetite (AM), and trimethylammonium dextran magnetite (TM)) with almost the same hydrodynamic diameters (50-55 nm) but different surface (zeta) potentials (−24 mV for CM, −15 mV for AM, and +2 mV for TM) were intratracheally injected to anesthetized ICR male mice at 10 weeks old using a nebulizing microsprayer containing 50 μL of MNPs. MPI images were acquired at 0.5, 6, 24, 72, and 168 hours after the injection of agents for each mouse. The retention value of the MNPs in the lungs was quantified from the average pixel value of the lungs in the MPI image. The retention value of TM in the lungs was significantly greater than that of AM at 6 and 168 hours after the injection of agents, and was significantly greater than that of CM at 72 and 168 hours after injection. The retention value of AM was significantly greater than that of CM at 168 hours after injection. The surface potential of MNPs affects the clearance of MNPs from the lungs due to MCT, suggesting that the retention of MNPs in the lungs can be controlled by manipulating the surface potential of MNPs. MPI will be useful for the visual and quantitative assessment of MCT, because MPI allows for repeated and long-term studies with a single injection of MNPs and with no radiation exposure.