Bifunctional Au–Fe₃O₄ Nanoheterodimers Acting as X-ray Protector in Healthy Cells and as X-ray Enhancer in Tumor Cells

Abstract

Bifunctional Au–Fe3O4 nanoheterodimers were synthesized by thermally decomposing Fe­(III)­oleate on gold nanoparticles followed by functionalizing with tiron, 2,3-dihydroxybenzoic acid, or caffeic acid. These catechol derivatives are antioxidative and thus are predicted to function as superoxide scavengers. In particular, caffeic acid lost its antioxidant capacity, although it was covalently linked through its carboxyl moiety to the Fe3O4 surface. Tiron was shown to bind via its catechol group to the Au–Fe3O4 nanoheterodimers, and 2,3-dihydroxybenzoic was just physisorbed between the oleic acid surface structures. Caffeic-acid stabilized Au–Fe3O4 nanoheterodimers turned out to act as X-ray protector in healthy cells but as X-ray enhancing agents in cancer cells. Furthermore, these functionalized Au–Fe3O4 nanoheterodimers were found to inhibit the migratory capacity of the cancer cells.

Caffeic Acid, Quercetin and 5-Fluorocytidine-Functionalized Au-Fe3O4 Nanoheterodimers for X-ray-Triggered Drug Delivery in Breast Tumor Spheroids

“…In this study, we show that surface-bound caffeic acid and quercetin act as X-radiation-enhancing agents in MCF-7 based MCTS, but they protect MCF-10 A MCTS against X-rays. These results are consistent with results obtained from analogous experiments performed on the respective 2D cell cultures and are ascribed to the particular cell-specific redoxactive properties of caffeic acid and quercetin [21]. In comparison, the effectiveness of 5-fluorocytidine-functionalized Au-Fe 3 O 4 NHDs in X-ray irradiated MCTS did not only consist in enhanced ROS production but also in the X-ray-induced release of 5-fluorocytidine, which damages tumor cells as an anticancer drug [32,33].…”

“…Biocompatibility and water dispersibility of the Au-Fe 3 O 4 nanoheterodimers were obtained by partial exchange of the oleylamine and oleic acid ligands by caffeic acid, quercetin or 5-fluorocytidine. Details of the procedure were given by S. Klein et al [ 21 ].…”

“…In former studies on monolayer cell cultures [ 20 , 21 , 22 ], we could prove that Au-Fe 3 O 4 nanoheterodimers (NHDs) performed as excellent X-radiation dose enhancing agents in tumor cells. Both, the gold and Fe 3 O 4 components were shown to contribute to the enhancement of the X-ray efficacy in complementary ways.…”

“…X-ray irradiated gold nanoparticles, as consisting of high-Z atoms, emit secondary X-rays, Auger- or photoelectrons [ 23 , 24 , 25 , 26 ], whereas the surface Fe 2+ cations catalyzed the Fenton reaction so that highly toxic • OH radicals are generated [ 27 , 28 , 29 ]. We reported that caffeic-acid functionalized Au-Fe 3 O 4 NHDs perform as radiosensitizers in breast cancer cells but acted as radioprotectors in healthy breast epithelial cells in 2D cell cultures [ 21 ].…”

Gold-based Inorganic Nanohybrids for Nanomedicine Applications

“…Due to the surface plasmon sensitization effect of Au shell, a 1.5-fold enhanced 1 O 2 generation by RB was detected. Furthermore, Au-Fe 3 O 4 nanocomposites are also efficient ROS generating agents with their intrinsic enzyme-mimic characteristics 144 - 146 . By deliberately designing hybrid nanostructures with multi-enzymatic activities to achieve cascade reactions, high chemo-dynamic therapeutic efficiency has been demonstrated using inorganic nanohybrids.…”