Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin

The purpose of this study was to construct and characterize iron oxide nanoparticles (IONP(CO)) for intracellular delivery of the anthracycline doxorubicin (DOX; IONP(DOX)) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONP(DOX) within 24 h (100% at 70 h). Efficient internalization of IONP(DOX) and IONP(CO) in HeLa cells occurred through pino- and endocytosis, with both IONP accumulating in a perinuclear pattern. IONP(CO) were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL IONP(CO). Treatment with IONP(DOX) resulted in a concentration- and time-dependent decrease in cell proliferation (IC(50) = 27.5 ± 12.0 μg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONP(CO) (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONP(DOX) efficiently delivered DOX resulting in increased cell death vs IONP(CO).