The
X-radiation enhancing
effect of caffeic acid-functionalized
Au–Fe3O4, Pt–Fe3O4, and Pd–Fe3O4 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–Fe3O4 and
Pt–Fe3O4 NHD-loaded MCF-7 MCTS significantly
decreased in volume after being exposed to fractionated irradiation,
whereas intracellular Au–Fe3O4 and Pt–Fe3O4 NHDs promoted the growth of the irradiated MCF-10A
MCS. Moreover, Au–Fe3O4 and Pt–Fe3O4 NHDs were shown to impede ROS formation and
inhibit DNA strand breakage in the noncancerous MCF-10A cells. On
the other hand, the Pd–Fe3O4 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–Fe3O4 and Pt–Fe3O4 NHDs performed as excellent X-radiation enhancing
agents in breast tumor cells, while they protect healthy breast epithelial
cells against X-radiation.
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