Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin
Roxana Cristina Popescu, Diana Savu, I. A. Dorobantu, Bogdan Ştefan Vasile, Hiltraud Hosser, A. Boldeiu, Mihaela Temelie, M. Straticiuc, D. Iancu, Ecaterina Andronescu, Frederik Wenz, Frank A. Giordano, Carsten Herskind, Marlon R. Veldwijk
Abstract
Abstract 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 .