Chemists from the Mass. Institute of Technology developed a nanoparticle that they can pack with 3 or more drugs to create custom combination therapies for cancer, according to a study published this week in the Journal of the American Chemical Society.
The team also revealed that cisplatin, a powerful anti-cancer drug, doesn’t work using the same DNA-damaging mechanism when delivered via nanoparticle compared to traditional methods.
The team uses a unique nanoparticle production method, which they 1st reported in 2014. Instead of trying to load the drugs onto nanoparticles that are already built, they create the nanoparticles from building blocks already containing the drugs. This gives them more precise control over the structure of the nanoparticle and the dosage of each drug, they argue.
“We can take any drug, as long as it has a functional group [a group of atoms that allows a molecule to participate in chemical reactions], and we can load it into our particles in exactly the ratio that we want, and have it release under exactly the conditions that we want it to,” senior author Jeremiah Johnson explained to MIT News. “It’s very modular.”
The researchers delivered doses of 3 different cancer-fighting drugs – cisplatin, doxorubicin and camptothecin – to mice and observed that ovarian tumors shrank among mice that received treatment. The team also found that survival rates were higher for treated mice than untreated mice, with fewer side effects.
To understand how the nanoparticles affected the cells, the team measured the more than 100 genes involved in the programmed cell death triggered by cancer drugs. Camptothecin and doxorubicin destroyed DNA using their usual pathways, but cisplatin exhibited a mechanism characterized by a different cancer drug, known as oxaliplatin.
Johnson suggested that this could be a more widespread problem than once thought, since many research teams attach cisplatin to nanoparticles in the same way.
Johnson’s lab is working on a nanoparticle that uses cisplatin’s usual mechanism, as well as high-capacity nanoparticles with a drug combination for pancreatic cancer.