MIT Chemists Design Multidrug Nanoparticle to Treat Cancer

(Image: Misael Moreno/Unsplash) When it comes to treating cancer, groups of synergistic drugs are often more effective than standalone drugs. But coordinating the delivery of multiple drugs is easier said than done. Drugs’ molecular properties tend to differ, making it difficult to ensure that pharmaceuticals make it to their destinations without losing effectiveness along the way. An all-new multidrug nanoparticle might be the solution. A team of researchers at MIT has created a “molecular bottlebrush” capable of delivering any number of drugs at the same time.

Drug-loaded nanoparticles—or ultrafine particles ranging from one to 100 nanometers in diameter—prevent treatments from being released prematurely, which ensures that the drug reaches its destination before beginning to do its job. This means nanoparticles carrying cancer treatments can collect at the tumor site, facilitating the most effective treatment possible. There is, of course, one caveat: Only a few cancer-treating nanoparticles have been approved by the FDA, and only one of those is capable of carrying more than one drug.

MIT’s molecular bottlebrush, detailed Thursday in the journal Nature Nanotechnology, challenges that. Chemists start by inactivating drug molecules by binding and mixing them with polymers. The result is a central “backbone” with several spokes. All it takes to activate the inactivated drugs sitting along the backbone is a break in one of those spokes. This unique design is what enables the new nanoparticle to carry (and thus deliver) multiple drugs at a time.

(Image: Detappe et al/Nature Nanotechnology/MIT)

The team tested the molecular bottlebrush in mice with multiple myeloma, a type of cancer that targets the body’s plasma cells. They loaded the nanoparticle with just one drug: bortezomib. On its own, bortezomib usually gets stuck in the body’s red blood cells; by hitching a ride on the bottlebrush, however, bortezomib accumulated in the targeted plasma cells.

The researchers then experimented with multidrug combinations. They tested three-drug bottlebrush arrangements on two mouse models of multiple myeloma and found that the combinations slowed or stopped tumor growth far more effectively than the same drugs delivered sans bottlebrush. The team even found that solo bortezomib, which is currently approved only for blood cancers and not solid tumors, was highly effective at inhibiting tumor growth in high doses.

Through their startup Window Therapeutics, the researchers hope to develop their nanoparticle to the point that it can be tested through clinical trials.

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