Fluorescent ZnO for imaging and induction of DNA fragmentation and ROS-mediated apoptosis in cancer cells.

Abstract

Fluorescein isothiocyanate (FITC)-encapsulated ZnO nanocomposite has been synthesized using the soft chemical approach. X-ray diffraction reveals the formation of highly crystalline single-phase hexagonal wurtzite nanostructure. TEM and SEM micrographs indicate the formation of spherical porous nanoassembly of ZnO of size ∼ 100-400 nm. On the other hand, FITC-ZnO nanocomposite is spherical and porous but with a uniform size of ∼150 nm. The size of single particles is ∼20 nm for the ZnO nanoassembly and ∼15 nm for FITC-ZnO nanocomposite. The UV-visible, fluorescence, FTIR and XPS spectra confirm the formation of FITC-ZnO nanocomposite. The FITC-ZnO nanocomposite demonstrates excellent selectivity in preferential killing of cervical (HeLa) and breast (MCF-7) cancer cells with minimal toxicity to normal fibroblast cells (L929). Apoptotic cells are observed and analyzed by confocal microscopy and flow cytometry. Our results show that cytotoxicity of FITC-ZnO nanocomposite towards cancer cells is due to the generation of reactive oxygen species (ROS) and preferential dissolution of Zn2+ ions in an acidic cancer microenvironment. Furthermore, generated ROS and dissolved Zn+2 ions induce cellular apoptosis, DNA fragmentation, and depolarization of mitochondrial membrane and cell cycle arrest in S phase. The FITC encapsulated multifunctional ZnO nanocomposite can be used as smart nanostructures for cell imaging and cancer therapy.