Background: Due to the potential advantages of Gadolinium Nanoparticles (NPs) over gadolinium elements,
gadolinium based NPs are currently being explored in the field of MRI. Either in elemental form or nanoparticulate
form, gadolinium toxicity is believed to occur due to the deposition of gadolinium ion (designated as Gd3+ ion
or simply G ion).
Objective: There is a serious lack of literature on the mechanisms of toxicity caused by either gadolinium-based NPs
or ions. Breast cancer tumors are often subjected to MRIs, therefore, human breast cancer (MCF-7) cells could serve
as an appropriate in vitro model for the study of Gadolinium Oxide (GO) NP and G ion.
Methods: Cytotoxicity and oxidative damage was determined by quantifying cell viability, cell membrane damage,
and Reactive Oxygen Species (ROS). Intracellular Glutathione (GSH) was measured along with cellular Total Antioxidant
Capacity (TAC). Autophagy was determined by using Monodansylcadaverine (MDC) and Lysotracker Red
(LTR) dyes in tandem. Mitochondrial Membrane Potential (MMP) was measured by JC-1 fluorescence. Physicochemical
properties of GO NPs were characterized by field emission transmission electron microscopy, X-ray diffraction,
and energy dispersive spectrum.
Results: A time- and concentration-dependent toxicity and oxidative damage was observed due to GO NPs and G
ions. Bax/Bcl2 ratios, FITC-7AAD double staining, and cell membrane blebbing in phase-contrast images all suggested
different modes of cell death induced by NPs and ions.
Conclusion: In summary, cell death induced by GO NPs with high aspect ratio favored apoptosis-independent cell
death, whereas G ions favored apoptosis-dependent cell death.