Preparation of iron oxide nanoparticles functionalized with Y-shaped ligands for brain tumor targeting

In this study, we developed functionalized iron oxide nanoparticles for brain tumor targeting. The iron oxide (Fe₃O₄) particles were stabilized with pluronic F127 and coupled with dopamine-terminated Y-shaped ligands (Tat peptide and transferrin) as a result of the noncovalent conjugation of dopamine (of Y-shaped ligands) and the iron oxide nanoparticles. Here, the hydrophobic domain of pluronic F127 coated on the iron oxide nanoparticles enabled the absorption of a model photosensitizing antitumor drug (chlorin e6) in the core/shell interface of the nanoparticles. The experimental results demonstrated that the Y-shaped ligands on the nanoparticles enabled a significant enhancement of in vitro/in vivo cellular uptake for human primary glioblastoma U87-MG cells as a result of multivalent endocytosis by Y-shaped ligands (transferrin receptor-mediated endocytosis and the following Tat peptide-mediated cellular interaction). Furthermore, the Ce6-loaded nanoparticles showed significant enhancement of in vitro/in vivo photodynamic U87-MG cell ablation under light illumination.