Transition metal oxide nanoparticles are effective in inhibiting lung cancer cell survival in the hypoxic tumor microenvironment

• Fe2O3, NiO, CuO nanoparticles were synthesized and characterized using SEM, XRD and FTIR.
• Anticancerous activity of these nanoparticle was tested against A549 lung cancer cell lines.
• Cell viability of lung cancer cells was compromised in both normoxia and hypoxia.
• ROS generation was shown to contribute to cellular toxicity in CuO, but not NiO and Fe2O3.
• These nanoparticles showed efficacy both in normoxic and hypoxic environment.

BackgroundThe transition metal oxide nanoparticles are in focus for their anti-cancer potential. In this study we have synthesized and characterized CuO, NiO and Fe2O3 nanoparticles and, investigated their cytotoxic potential in the heterogeneous tumour microenvironment.MethodsNanoparticles were synthesized by aqueous precipitation method and characterized with UV-Visible spectrophotometer, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and X-ray diffraction (XRD). Cell viability of lung cancer cells (A549) grown in normoxia (18%O2) and hypoxia (1%O2) was determined for all nanoparticles. The mechanism of cell death was assessed by nuclear morphological analysis, flow cytometry analysis and western blotting. Generation of intracellular ROS in treated cells and its contribution to cell viability was determined.ResultsThe synthesized metal oxide nanoparticles were successfully characterized with SEM, spectroscopy and X-ray diffraction patterns. Cell viability of lung cancer cells was compromised in both normoxia and hypoxia. ROS generation was shown to contribute to cellular toxicity in CuO, but not NiO and Fe2O3.ConclusionWe have shown the therapeutic potential of CuO, NiO and Fe2O3 nanoparticles in non small cell lung cancer cells cultured in hypoxia, a relevant feature of solid tumors along with normoxia. The newly synthesized nanoparticles showed efficacy in both conditions.General significanceHypoxia drives metabolic alterations and epigenetic modifications in the tumor microenvironment. By using conditions that mimic tumour microenvironment, this study expands the possibility of using metal oxide nanoparticles as a therapeutic agent for lung cancer treatment.

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