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

R C Popescu; D Savu; I Dorobantu; B S Vasile; H Hosser; A Boldeiu; M Temelie; M Straticiuc; D A Iancu; E Andronescu; F Wenz; F A Giordano; C Herskind; M R Veldwijk

doi:10.1038/s41598-020-67207-y

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

Sci Rep. 2020 Jun 29;10(1):10530. doi: 10.1038/s41598-020-67207-y.

Authors

R C Popescu^{1

2

3}, D Savu⁴, I Dorobantu¹, B S Vasile², H Hosser⁵, A Boldeiu⁶, M Temelie¹, M Straticiuc⁷, D A Iancu⁷, E Andronescu², F Wenz⁸, F A Giordano³, C Herskind³, M R Veldwijk⁹

Affiliations

¹ "Horia Hulubei" National Institute for Research and Development in Physics and Nuclear Engineering, Department of Life and Environmental Physics, Reactorului 30, 077125, Magurele, Romania.
² Politehnica University of Bucharest, Department of Science and Engineering of Oxide Materials and Nanomaterials, Polizu 1-7, 011061, Bucharest, Romania.
³ Heidelberg University, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Department of Radiation Oncology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
⁴ "Horia Hulubei" National Institute for Research and Development in Physics and Nuclear Engineering, Department of Life and Environmental Physics, Reactorului 30, 077125, Magurele, Romania. dsavu@nipne.ro.
⁵ Heidelberg University, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Center for Biomedicine and Medical Technology, Department of Anatomy and Developmental Biology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
⁶ National Institute for Research and Development in Microtechnologies, Laboratory of Nanobiotechnology, Erou Iancu Nicolae 12A, 077190, Bucharest, Romania.
⁷ "Horia Hulubei" National Institute for Research and Development in Physics and Nuclear Engineering, Department of Applied Nuclear Physics, Reactorului 30, 077125, Magurele, Romania.
⁸ University Medical Center Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
⁹ Heidelberg University, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Department of Radiation Oncology, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany. Marlon.Veldwijk@medma.uni-heidelberg.de.

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 (IC₅₀ = 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibiotics, Antineoplastic / administration & dosage*
Biological Transport / drug effects
Cell Survival / drug effects*
Doxorubicin / administration & dosage*
Drug Delivery Systems*
Endocytosis / drug effects*
HeLa Cells
Humans
Magnetite Nanoparticles / administration & dosage*

Substances

Antibiotics, Antineoplastic
Magnetite Nanoparticles
Doxorubicin