Anticancer Activity of ZnO Nanoparticles against Human Small-Cell Lung Cancer in an Orthotopic Mouse Model

Abstract

Small-cell lung cancer, a highly malignant form of lung cancer, often responds to first-line treatments but relapses in most cases with resistance to further treatments. We tested zinc oxide (ZnO) nanoparticles against small-cell lung cancer and other cancer cell lines, in light of reported anticancer effects in vitro. Because of a strong safety record, ZnO nanoparticles are frequently used in biomedical research, including in cellular imaging and drug delivery, and have been used for many years in several commercial products such as skin care agents. Strikingly, ZnO nanoparticles were genotoxic against small-cell lung cancer cells, resulting in low viability, even in cells orthotopically grafted onto mouse models. However, the nanoparticles were less cytotoxic against normal lung-derived cells and did not elicit observable adverse effects after intravenous administration. ZnO nanoparticles were also found to induce highly reactive oxygen species and DNA leakage from nuclei. This study is the first comprehensive evaluation of the anticancer effects of ZnO nanoparticles in vitro and in vivo and highlights new therapeutic opportunities against small-cell lung cancer.

Tumoricidal and Bactericidal Properties of ZnONPs Synthesized Using Cassia auriculata Leaf Extract

“…Furthermore, the crystallinity observed in the XRD spectrum was complemented by high-resolution TEM (HRTEM) studies. As shown in Figure 7 b, the observed diffraction lattice fringes in ZnONPs show d-spacing with an inter-planar distance of 0.260 nm between two fringes, which corresponds to d-spacing of the (002) crystal plane of ZnO [ 20 ]. Moreover, it has been reported that a decrease in the particle size increases the functionality of antimicrobial and anticancer agents due to the larger surface-to-volume ratio [ 13 ].…”

“…Meanwhile, zinc oxide nanoparticles (ZnONPs), a versatile drug delivery tool, have recently been reported to possess significant tumoricidal activity via ROS generation or the caspase-8 and p53 pathway [20][21][22]. However, a better understanding of the mechanistic model and the resultant cellular consequences is essential.…”

SnO2-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway

“…First, we exposed the cells with a range of concentrations (0-200 µg/mL) of ZnO NPs, SnO 2 -ZnO NPs, and SnO 2 -ZnO/rGO NCs for 24 h for cell viability assay. On the basis of cell viability results, we have chosen three moderate concentrations (10,25, and 50 µg/mL) of these samples for further experiments. For microscopic study we have chosen one concentration (50 µg/mL) of prepared samples.…”

“…Due to unique physiochemical characteristics ZnO NPs have shown inherent selective toxicity against cancer cells while posing minimum effects to the normal cells. [9][10][11] ZnO NPs induce apoptosis in cancer cells through the generation of ROS and depletion of mitochondrial membrane potential (MMP) 12,13 Manipulation in intracellular ROS generation is a probable way to irreversibly damage cancerous cells selectively without applying much harm to normal cells. The ROS-generating potential of ZnO NPs is associated with its optical properties.…”

Effect of Zinc Supplementation on the Serum Metabolites Profile at the Early Stage of Breast Cancer in Rats

“…Furthermore, the anti-cancer effect of biosynthesized Zn NP was also found by Raajshree et al in the murine model of Dalton’s lymphoma ascites [ 16 ]. Tanino et al reported genotoxicity of ZnO NP and low viability of small-lung cancer in mice in response to treatment [ 17 ]. In most cases, effects on normal cells were minimal, and effective tumor inhibition was found.…”