UGA Scientists Enhance Chemotherapy Activity 17x With Nanoparticles
Scientists from the University of Georgia reported that they have developed a new formulation of cisplatin using nanoparticles and increased its activity 17 times more than in its current form.
Cisplatin is a commonly used chemotherapy drug for the treatment of bladder, ovarian, cervical, lung, and testicular cancer. While effective, many cancerous cells develop resistance to cisplatin over the course of therapy.
To overcome the cancer cells’ tendency to develop resistance, Shanta Dhar, assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and Rakesh Pathak, a postdoctoral researcher working in Dhar's lab, developed a modified formulation of cisplatin. They called it Platin-M and designed it to attach to the mitochondria of cancer cells. Professor Dhar described the mitochondria as a ‘powerhouse’ of cells, producing the energy necessary for growth and reproduction. Targeting the mitochondria directly disrupts the cancer cells’ survival. “This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive,” she said.
To target the mitochondria, Dhar’s student Sean Marrache trapped Platin-M in a nanoparticle designed to seek out the cell part and release the drug. Once Platin-M penetrated the cell, it interferes with the mitochondria’s DNA and triggers cell death. The research team tested the new formulation on neuroblastoma cells in preliminary experiments using a cisplatin-resistant cell culture. They found that Platin-M nanoparticles were 17 times more active than the original drug alone. Pathak said, “This technique could become a treatment for a number of cancers, but it may prove most useful for more aggressive forms of cancer that are resistant to current therapies.”
The researchers said they are in the process of developing more extensive safety trials for Platin-M. A study of their work entitled ‘Detouring of cisplatin to access mitochondrial genome for overcoming resistance’ was published in the Proceedings of the National Academy of Sciences.