Publication Type:

Journal Article

Source:

Nanoscale, Volume 3, Number 9, p.3657-3669 (2011)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-80052575055&partnerID=40&md5=3672d8fcf0ccafd0f7d27cbbec480f4a

Keywords:

Acidic microenvironment, apoptosis, article, Cancer cell lines, Cancer cells, Cell culture, Cell death, Cell Line, Cell membranes, Cell-cycle arrest, chemistry, confocal microscopy, Diseases, Dissolution, drug effect, Drug Resistance, Endothelial cells, flow cytometry, Glycols, human, Human dermal fibroblasts, Human umbilical vein endothelial cells, Humans, Hydrogen-Ion Concentration, macrogol derivative, Membrane Potential, metabolism, metal nanoparticle, Metal Nanoparticles, Microenvironments, Mitochondria, Mitochondrial, mitochondrial membrane potential, Mitochondrial membranes, Mitochondrial superoxide, Multiple stress, Nanocrystals, neoplasm, Neoplasms, Oxygen, pathology, pH, Polyethylene glycols, Preferential dissolution, Primary cells, reactive oxygen metabolite, Reactive Oxygen Species, Silica, Solid tumors, Surface chemistry, toxicity, tumor microenvironment, Zinc oxide, ZnO, ZnO nanocrystal

Abstract:

The microenvironment of cancer plays a very critical role in the survival, proliferation and drug resistance of solid tumors. Here, we report an interesting, acidic cancer microenvironment-mediated dissolution-induced preferential toxicity of ZnO nanocrystals (NCs) against cancer cells while leaving primary cells unaffected. Irrespective of the size-scale (5 and 200 nm) and surface chemistry differences (silica, starch or polyethylene glycol coating), ZnO NCs exhibited multiple stress mechanisms against cancer cell lines (IC50 ∼150 μM) while normal human primary cells (human dermal fibroblast, lymphocytes, human umbilical vein endothelial cells) remain less affected. Flow cytometry and confocal microscopy studies revealed that ZnO NCs undergo rapid preferential dissolution in acidic (pH ∼5-6) cancer microenvironment causing elevated ROS stress, mitochondrial superoxide formation, depolarization of mitochondrial membrane, and cell cycle arrest at S/G2 phase leading to apoptosis. In effect, by elucidating the unique toxicity mechanism of ZnO NCs, we show that ZnO NCs can destabilize cancer cells by utilizing its own hostile acidic microenvironment, which is otherwise critical for its survival. © The Royal Society of Chemistry 2011.

Notes:

cited By 28

Cite this Research Publication

A. Sasidharan, Chandran, P., Menon, D., Raman, S., Nair, S., and Koyakutty, M., “Rapid dissolution of ZnO nanocrystals in acidic cancer microenvironment leading to preferential apoptosis”, Nanoscale, vol. 3, pp. 3657-3669, 2011.