Jul 18, 2008
Preferential cancer cell killing using ZnO nanoparticles
One of the greatest challenges preventing advances in new therapeutic options for treating cancer is the inability of anti-cancer drugs to effectively differentiate between cancerous and normal healthy body cells. Many commonly used chemotherapeutic drugs target rapidly dividing cells but suffer from a relatively low therapeutic index, which is the ratio of toxic dose to effective dose. This limitation frequently leads to systemic toxicity and debilitating adverse effects in normal body tissues, which limits the amount of drug that can be administered and reduces anti-tumor efficacy.
In a recent study published in Nanotechnology, it was found that ZnO nanoparticles have intrinsic properties that enable them to preferentially kill cancerous T-cells while sparing healthy normal cells. The preferential toxicity of ZnO nanoparticles towards cancerous T-cells is of substantial magnitude (~28–35 times), especially in comparison with ex vivo indices of ≤10 reported for other commonly used chemotherapeutic agents using similar assays.
Mechanisms of nanoparticle-induced cell death involve the generation of reactive oxygen species, and protection against cytotoxicity can be largely prevented by chemical inhibitors of reactive oxygen species. Preferential cytotoxicity also appears to be related to the proliferative capacity of the cell as normal non-dividing cells that are stimulated to proliferate demonstrate an increased sensitivity to ZnO nanoparticle-induced death.
The inherent differential toxicity of ZnO nanoparticles against rapidly dividing cancer cells raises exciting opportunities for their potential use as anti-cancer agents, and the selectivity of these nanomaterials may be expected to be even further enhanced by linking tumor targeting proteins, such as monoclonal antibodies, peptides and small molecules to tumor-associated proteins, or by using nanoparticles for drug delivery. These future directions are currently being explored by the research team as well as altering nanoparticle engineering design to further improve their inherent cell selectively against cancer cells while sparing normal healthy body cells and increasing their overall efficacy.
About the author
D Wingett is an associate professor and associate chair of the Department of Biological Sciences at Boise State University. A Punnoose is an associate professor in the Department of Physics at Boise State University.