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

ABSTRACT

The purpose of this study was to construct and characterize iron oxide nanoparticles (IONPCO) for intracellular delivery of the anthracycline doxorubicin (DOX; IONPDOX) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONPDOX within 24 h (100% at 70 h). Efficient internalization of IONPDOX and IONPCO in HeLa cells occurred through pino- and endocytosis, with both IONP accumulating in a perinuclear pattern. IONPCO were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL IONPCO. Treatment with IONPDOX resulted in a concentration- and time-dependent decrease in cell proliferation (IC50 = 27.5 ± 12.0 µg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONPCO (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONPDOX efficiently delivered DOX resulting in increased cell death vs IONPCO.