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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 .

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