In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe₃O₄‐TiO₂ nanoparticles in human liver cells

Abstract

Recent studies show that Janus Fe O -TiO nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe O -TiO nanoparticles, an in vitro study using a human liver cell line HL-7702 cells was conducted. For comparison, the Janus Fe O -TiO NPs parent material TiO NPs was also evaluated. Results showed that both Fe O -TiO NPs and TiO NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC-1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO NPs induced slightly higher cytotoxicity than Fe O -TiO NPs in HL7702 cells. Western blotting indicated that both TiO NPs and Fe O -TiO NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe O -TiO NPs induced higher signal protein expressions than TiO NPs under a high treatment dose. However, under a low dose (6.25 μg/cm ), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe O -TiO NPs and TiO NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe O -TiO NPs.

<p>The Toxicity Of Metallic Nanoparticles On Liver: The Subcellular Damages, Mechanisms, And Outcomes</p>

“…By regulating the expression of Bax and Bcl-2, Ag NPs destroyed mitochondrial membrane potential, induced cytochrome c release in cytoplasm, and activated caspase-9 and caspase-3 27. Exposure of the liver cells (HL7702 cells, CHANG cells, HepG2 cells) to MNPs (Cs-Ag NPs, rGO-Ag NPs, TiO 2 NPs, Fe 3 O 4 -TiO 2 NPs) has been proved to have the same damage effects 23,95,96…”

“…The time-dependent ROS production data from the current study illustrates that ROS can be used as an early and potent diagnostic marker for SPION-induced toxicity as well as other nanotoxicological inquiries in the liver.76Fe 3 O 4 -TiO 2 20–25–HL-7702Ti: 0; 6.25; 15.625 25 µg/cm 2 12 hrsFe 3 O 4 -TiO 2 NPs induced cellular ROS generation, reduced cell viability, and induced apoptosis in a dose-dependent manner in HL7702 cells. Mitochondrial membrane was damaged and cytochrome c was released, followed by regulation of apoptosis-related proteins.96 Abbreviations: HSCs, hepatic stellate cells; MMP, matrix metalloprotein; IC50, half-maximal inhibitory concentration; PVA, Polyvinyl alcohol; GSH, glutathione; NLRP3:NLRs, pyrin domain containing 3; LC50, median lethal concentration; MAPK, mitogen-activated protein kinase; AKT, protein kinase B; CHANG, human Chang liver cells; LD50, median lethal dose; SPION, superparamagnetic iron oxide nanoparticles.…”

89Zr Labeled Fe3O4@TiO2 Nanoparticles: In Vitro Afffinities with Breast and Prostate Cancer Cells

“…X‐radiation was made in the same geometry as photodynamic therapy. While photodynamic therapy is carried out through a selective reactive effect on a single molecule, the radiolysis mechanisms through ionized, excited, and radical series formed during the water's radiolysis are more effective in radiotherapy …”

Utilizing Iron for Targeted Lipid Peroxidation as Anticancer Option of Integrative Biomedicine: A Short Review of Nanosystems Containing Iron

“…Janus Fe 3 O 4 -TiO 4 nanoparticles, a potential agent for magnetic resonance imaging and PDT, when used at a higher dose (25 µg/cm 2 ), alter cellular redox homeostasis of normal hepatic cells inducing lipid peroxidation while decreasing cell viability and ATP levels. However, if used at a lower dose (6.25 µg/cm 2 ), such effects are not observed [90]. Additionally, particle size and different coatings on their surface can be detrimental for their activity [91].…”