A scientific team at MIT has developed a bottlebrush-shaped nanoparticle that can deliver combinations of drugs for synergistic efficacy. The particles contain a central backbone and demonstrate side-chains that sprout from this backbone, similar to the handle and bristles of a bottlebrush. Several drugs can be mixed in different ratios and combined with polymer building blocks during particle preparation, and then the drugs are released from the particle when the bristles are enzymatically cleaved from the particle body. The researchers have tested the particles in their ability to deliver combinations of anti-cancer drugs and they have demonstrated synergistic efficacy that would be difficult to achieve with combinations of freely delivered drugs.
Administering several drugs at once can produce synergistic efficacy, something which is sometimes used to good effect in treating cancer. However, finding these combinations and making sure that the drugs arrive at the target site at roughly the same time to enable this effect is difficult.
“There’s a lot of interest in finding synergistic combination therapies for cancer, meaning that they leverage some underlying mechanism of the cancer cell that allows them to kill more effectively, but oftentimes we don’t know what that right ratio will be,” said Jeremiah Johnson, a researcher involved in the study.
To address this, these researchers have developed a nanoparticle that can easily carry a mixture of drugs, with a focus on cancer for now. The idea is that these particles allow the drugs to arrive and act on a tumor at the same time, facilitating their potential to produce synergistic efficacy.
“If we want to make a bottlebrush that has two drugs or three drugs or any number of drugs in it, we simply need to synthesize those different drug conjugated monomers, mix them together, and polymerize them,” added Johnson. “The resulting bottlebrushes have exactly the same size and shape as the bottlebrush that only has one drug, but now they have a distribution of two, three, or however many drugs you want within them.”
So far, the researchers have tested the particles in mice with multiple myeloma. They found that bottlebrush particles that were loaded with three different anti-cancer drugs demonstrated significantly increased anti-cancer efficacy compared with a combination of freely delivered drugs at the same ratio, and mixtures of bottlebrush particles containing one of each of the drugs in each particle.
Study in journal Nature Nanotechnology: Molecular bottlebrush prodrugs as mono- and triplex combination therapies for multiple myeloma