Normally, positively charged gold nanoparticles are toxic to cells and can lead to cell death. Malignant cancer cells have a way around this toxicity, but now researchers may have discovered how to use these nanoparticles in a potential targeted cancer therapy.

Researchers at the Mayo Clinic, who published their findings in The Journal of Biological Chemistry, say they've found out how ovarian cancer cells avoid being killed by positively charged gold nanoparticles, and how to make the cells susceptible to the nanoparticles' toxic effects.

"Gold nanoparticles can have many medical uses, from imaging and aiding diagnoses to delivering therapies," the Mayo Clinic says in a press release. "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." However, this can be done, however, if the cancer cells in question are made susceptible to the nanoparticles' toxic effects.

Usually, nanoparticles kill cells by increasing cellular levels of calcium ions, which is toxic. But in malignant ovarian cancer cells have an abundance of a regulatory gene called MICU1, which forms transporters that prevent calcium build-up, researchers found. Thus, in cancer cells, the abundance of MICU1 transporters moves calcium into the mitochondria, leaving the cells free of the detrimental effects of the nanoparticles.

Furthermore, the team found that inhibiting calcium transportation by MICU1 leads to stress in the cancer cells' endoplasmic reticulum membrane network, sensitizing the cancer cells to the toxic effects of the gold nanoparticles. This can be achieved through pharmacological means or through using small interfering RNA.

The researchers also found that silencing MICU1 in the ovarian cancer cells in turn decreases expression of the Bcl-2 protein, which has been implicated in the development of a number of cancers. Repressing the Bcl-2 protein also increases levels of the caspace-3 protein and cytosolic cytochrom C, both of which are proteins involved in the initiation and execution of cell death. 

These effects are further enhanced by the presence of positively charged gold nanoparticles, initiating the cycle of cell death, the researchers discovered.

"This study highlights the potential of nanomaterials as a tool to broaden our understanding of cellular processes, establishes MICU1 as a novel regulator of the apoptotic machinery in cancer cells and emphasizes the need to synergize nanoparticle design with understanding of mitochondrial machinery for enhancing targeted cellular toxicity," they add.

This relationship between gold nanoparticles and gene regulation in cancer cells could be integrated into nanotechnology develops to create new therapies.

 

Source: Arvizo, RR, Moyano, DF, Saha, S, et al. Probing Novel Roles of the Mitochondrial Uniporter in Ovarian Cancer Cells Using Nanoparticles. The Journal of Biological Chemistry. 2013. Accessed May 21, 2013.