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


METHODS
Nanoparticles 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.


RESULTS
The 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.


CONCLUSIONS
We 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.


CONCLUSIONS
Hypoxia 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.
Department of Genetics, University of Delhi South Campus, India.
Namita
N
Pandey
Department of Chemistry, Amity School of Applied Science, Amity University Haryana, India.
Shikha
S
Dhiman
Department of Genetics, University of Delhi South Campus, India. Electronic address: tapasya@south.du.ac.in.
Tapasya
T
Srivastava
Department of Chemistry, Amity School of Applied Science, Amity University Haryana, India; Centre for Nano Science and Technology, Amity University Haryana, India. Electronic address: sudip22m@gmail.com.
Sudip
S
Majumder
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles; D008855:Microscopy, Electron, Scanning; D010087:Oxides / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D020349:Surface Plasmon Resonance; D013818:Thermogravimetry; D028561:Transition Elements / Q000737:chemistry / Q000494:pharmacology*; D059016:Tumor Microenvironment; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; C468783:H2AX protein, human; D006657:Histones; D010087:Oxides; D017382:Reactive Oxygen Species; D028561:Transition Elements; D000071137:Poly (ADP-Ribose) Polymerase-1
Anticancerours activity; Hypoxia; Lung cancer; Transition metal oxide nanoparticles; Tumor microenvironment