Bottlebrush-shaped molecules carry drug combos to combat cancer
Scientists at MIT have developed bottlebrush-shaped molecules that can carry groups of different cancer drugs in just the right ratio. Tests in mice showed significantly improved outcomes compared to just giving the drugs loose.
Existing cancer drugs can be effective against the disease, but unfortunately they don’t always go exactly where they’re needed in the right amounts, leading to a range of toxic side effects. Groups of drugs can multiply the cancer-fighting potential – but it’s even harder to corral them to the target.
“If you inject three drugs into the body, the likelihood that the correct ratio of those drugs will arrive at the cancer cell at the same time can be very low,” said Jeremiah Johnson, co-senior author of the study. “The drugs have different properties that cause them to go to different places, and that hinders the translation of these identified synergistic drug ratios quite immensely.”
So the MIT team developed a type of molecule that could be modified to contain several types of drugs, in exactly the right ratios, keeping them inert until they reach the cancer cells. The drug molecules are bound to monomers, then it’s all mixed together so that those building blocks form polymers. This creates a kind of chain with the dormant drugs protruding off a central backbone, giving the molecule a bottlebrush shape.
The team first tested the bottlebrush drug carriers against cancer cells in lab dishes, to experiment with the most effective ratios of three cancer drugs used to treat multiple myeloma: bortezomib, an immune-stimulating drug called pomalidomide, and an anti-inflammatory called dexamethasone.
Once the researchers had identified the ideal ratios, they administered the drugs via bottlebrush molecules to mice with multiple myeloma. And sure enough, the bottlebrushes containing all three drugs significantly slowed tumor growth, compared to giving the drugs loose at the same ratios, or giving all three drugs within their own bottlebrushes.
The team also found that bottlebrushes containing just bortezomib performed better than when the drug is given loose. It also reduced side effects, since this drug can accumulate in and damage red blood cells as well as cancer cells.
As intriguing as the idea is, it’s worth keeping in mind that these studies are still in the very early stages, and results in mice don’t always carry across to humans. The researchers plan to continue developing the bottlebrushes for eventual clinical trials, as well as investigating other drug combos they could carry. That could include other therapeutics like antibodies and mRNA.
The research was published in the journal Nature Nanotechnology.
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