Positively charged gold nanoparticles are usually toxic to cells, but cancer cells somehow manage to avoid nanoparticle toxicity. Mayo Clinic researchers claim to have found out why and to have determined how to make the nanoparticles effective against ovarian cancer cells.
Their discovery is detailed in the current online issue of the Journal of Biological Chemistry.
"This study identifies a novel mechanism that protects ovarian cancer cells by preventing the cell death or apoptosis which should occur when they encounter positively charged nanoparticles," say the senior authors of this study, Priyabrata Mukherjee, a Mayo Clinic molecular biologist, and Dr. Y. S. Prakash, a Mayo Clinic anesthesiologist and physiologist.
Gold nanoparticles can have many medical uses, from imaging and aiding diagnoses to delivering therapies, the researchers say. In this case, using a special preparation to put positive ionic charges on the surface, the nanoparticle is intended to act as a targeted destructor of tumor cells while leaving healthy cells alone, they say.
The nanoparticles are supposed to kill cells by causing cellular calcium ion levels to increase, but researchers say they discovered that a regulatory protein in the mitochondria essentially buffers the rising calcium by transporting it into the mitochondria, thus subverting cell death. Cancer cells have an abundance of this transporter and may thus be protected from nanoparticle toxicity.
The research team claims to have discovered that if calcium uptake into the mitochondria is inhibited, cellular stress builds up, making the gold nanoparticles more effective in destroying cancer cells.
The researchers say that understanding how mitochondrial transport mechanisms work will help in the design of targeted therapies against cancer.