Pt-Fe 3 O 4 , Pd-Fe 3 O 4 , and Au-Fe 3 O 4 Nanoheterodimers and Their Efficacy as Radiosensitizers in Cancer Therapy.

The X-radiation enhancing effect of caffeic acid-functionalized Au-Fe 3 O 4 , Pt-Fe 3 O 4 , and Pd-Fe 3 O 4 nanoheterodimers (NHDs) on 2D and 3D breast tumor (MCF-7) and healthy breast epithelial (MCF-10A) cells was comprehensively examined by performing cell viability, reactive oxygen species (ROS) detection, enzyme activity, and clonogenic assays. Intracellular NHDs were observed to cause DNA fragmentation and to enhance superoxide and hydroxyl radical formation in MCF-7 cells when exposed to a single dose of 1 Gy. MCF-7-derived multicellular tumor spheroids (MCF-7 MCTS) and MCF-10A-derived multicellular spheroids (MCF-10A MCS) were incubated with the NHDs and irradiated with five daily doses of 2 Gy. The Au-Fe 3 O 4 and Pt-Fe 3 O 4 NHD-loaded MCF-7 MCTS significantly decreased in volume after being exposed to fractionated irradiation, whereas intracellular Au-Fe 3 O 4 and Pt-Fe 3 O 4 NHDs promoted the growth of the irradiated MCF-10A MCS. Moreover, Au-Fe 3 O 4 and Pt-Fe 3 O 4 NHDs were shown to impede ROS formation and inhibit DNA strand breakage in the noncancerous MCF-10A cells. On the other hand, the Pd-Fe 3 O 4 NHDs boosted X-radiation-induced damage of MCF-10 A cells, which was ascribed to impairment of the ROS scavenging enzyme activities. In summary, caffeic acid-functionalized Au-Fe 3 O 4 and Pt-Fe 3 O 4 NHDs performed as excellent X-radiation enhancing agents in breast tumor cells, while they protect healthy breast epithelial cells against X-radiation.