Fabrication and application of iron oxide-encapsulated PLGA nanoparticles with dual responsiveness to magnetic fields and light for nose-to-brain drug delivery

Abstract

Nose-to-brain delivery has been widely investigated as a potential strategy for glioma therapy. However, the nasal epithelial barrier remains a major obstacle to drug transport from the nasal cavity to the brain, particularly for macromolecular agents such as peptides, nucleic acids, and nanoparticles. Therefore, strategies to enhance epithelial permeability are required. In this study, we developed a drug delivery system to improve nose-to-brain transport through transcranial magnetic field application, with the aim of contributing to glioma treatment. Iron oxide nanoparticles (IONPs), which possess both superparamagnetic and photothermal properties, were utilized to enhance brain penetration and to enable photothermal therapy (PTT). IONPs were encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to form IONPs@PLGA, with an average size of approximately 200 nm. Transmission electron microscopy revealed that IONPs were located inside PLGA nanoparticles, and laser irradiation (660 nm) raised the temperature to 50 °C, suggesting that IONPs@PLGA generated sufficient heat to induce cancer cell death. Moreover, IONPs@PLGA were efficiently internalized by cells under a magnetic field, and laser irradiation induced strong cytotoxicity against C6 glioma cells. Notably, applying a magnetic field after intranasal administration increased brain accumulation by ∼2.5-fold, confirming enhanced delivery via magnetic targeting. In summary, we developed IONPs@PLGA, a dual magnetic- and light-responsive system, and demonstrated its potential to improve nose-to-brain delivery. Given their drug-loading capacity, IONPs@PLGA represent a promising platform for magnetically guided, non-invasive brain drug delivery.