Understanding the Role of Surface Charge in Cellular Uptake and X-ray-Induced ROS Enhancing of Au-Fe3O4 Nanoheterodimers

Stefanie Klein; Lisa M S Stiegler; Christina Harreiss; Luitpold V R Distel; Winfried Neuhuber; Erdmann Spiecker; Andreas Hirsch; Carola Kryschi

doi:10.1021/acsabm.8b00511

Understanding the Role of Surface Charge in Cellular Uptake and X-ray-Induced ROS Enhancing of Au-Fe₃O₄ Nanoheterodimers

ACS Appl Bio Mater. 2018 Dec 17;1(6):2002-2011. doi: 10.1021/acsabm.8b00511. Epub 2018 Nov 16.

Authors

Stefanie Klein¹, Lisa M S Stiegler², Christina Harreiss³, Luitpold V R Distel⁴, Winfried Neuhuber⁵, Erdmann Spiecker³, Andreas Hirsch², Carola Kryschi¹

Affiliations

¹ Department Chemistry and Pharmacy, Physical Chemistry I and ICMM, Friedrich-Alexander University of Erlangen-Nuremberg, Egerlandstr. 3, Erlangen D-91058, Germany.
² Department of Chemistry and Pharmacy, Institute of Organic Chemistry II, Friedrich-Alexander University of Erlangen-Nuremberg, Nikolaus-Fiebiger-Str. 10, Erlangen D-91058, Germany.
³ Institute of Micro- and Nanostructure Research and Center for Nanoanalysis and Electron Microcopy (CENEM), Friedrich-Alexander University of Erlangen-Nuremberg, Cauerstr. 6, Erlangen D-91058, Germany.
⁴ Department of Radiation Oncology, Friedrich-Alexander University of Erlangen-Nuremberg, Universitätsstr. 27, Erlangen D-91054, Germany.
⁵ Department of Anatomy, Chair of Anatomy I, Friedrich-Alexander University of Erlangen-Nuremberg, Krankenhausstr. 9, Erlangen D-91054, Germany.

PMID: 34996262
DOI: 10.1021/acsabm.8b00511

Abstract

Au-Fe₃O₄ nanoheterodimers were obtained by thermally decomposing iron oleate on presynthesized gold nanoparticles. Water solubility as well as surface charges were achieved by encapsulating the initially hydrophobic Au-Fe₃O₄ nanoheterodimers in a self-assembled bilayer shell formed either by 1-octadecylpyridinium, providing positive surface charges, or by 4-dodecylbenzenesulfonate, yielding a negatively charged surface. The surface charge and surface architecture were shown to control both the cellular entry and the intracellular trafficking of the Au-Fe₃O₄ nanoheterodimers. The positively charged (1-octylpyridinium-terminated) Au-Fe₃O₄ nanoheterodimers were internalized by both breast cancer cells (MCF-7) and epithelial cells (MCF-10 A), wherein they were electrostatically bound at the negatively charged membranes of the cell organelles and, in particular, adsorbed onto the mitochondrial membrane. The treatment of MCF-7 and MCF-10 cells with a fractional X-radiation dose of 1 Gy resulted into a large increase of superoxide production, which arose from the Au-Fe₃O₄ nanoheterodimer-induced mitochondrial depolarization. In contrast, the negatively charged (4-dodecylbenzenesulfonate-terminated) Au-Fe₃O₄ nanoheterodimers preferentially invaded the cancerous MCF-7 cells by direct permeation. X-ray treatment of MCF-7 cells, loaded with anionic Au-Fe₃O₄ nanoheterodimers, yielded the increase of both hydroxyl radical and cytoplasmic superoxide formation. The X-radiation-induced activation of the Fe₃O₄ surfaces, consisting of Fe²⁺ and Fe³⁺ cations, triggered the catalysis of the hydroxyl radical production, whereas superoxide formation presumably occurred through X-ray-induced photoelectron emission near the Au surface. Since hydroxyl radicals are highly cytotoxic and the negatively charged Au-Fe₃O₄ NHDs spare the healthy MCF-10A cells, these Au-Fe₃O₄ nanoheterodimers exhibit a higher potential for radiation therapy than the positively charged Au-Fe₃O₄ nanoheterodimers. Encouraging results from the clonogenic cell survival assay and DMF calculations corroborate the excellent performance of the anionic Au-Fe₃O₄ nanoheterodimers as an X-ray dosage enhancer.

Keywords: Au−Fe3O4 nanoheterodimers; radiation therapy; reactive oxygen species; self-assembled bilayer; surface charge.