Combining multiple drugs to treat cancer can be more effective than using a single drug, but determining the ideal combination and ensuring that the drugs reach their target can be difficult. MIT chemists have created a bottlebrush-shaped nanoparticle that can hold multiple drugs in adjustable ratios.
Using these particles, the researchers were able to deliver the optimal ratio of three cancer drugs for treating multiple myeloma. In a study on mice, the researchers found that the nanoparticles carrying the three drugs in the synergistic ratio they identified were more effective at shrinking tumors than when the drugs were given at the same ratio but not attached to a particle. This nanoparticle platform could be used to deliver drug combinations for various types of cancer.
Nanoparticles have the potential to deliver cancer drugs more effectively by accumulating at the tumor site and reducing toxic side effects. However, only a few nanoparticle drug formulations have been approved by the FDA to treat cancer, and only one of them carries more than one drug. Researchers at the Massachusetts Institute of Technology have been working on developing polymer nanoparticles that can carry multiple drugs for several years.
Bottlebrush-Shaped Nanoparticle
In a recent study, they focused on a bottlebrush-shaped particle. The team created these particles by binding drug molecules to polymer building blocks and mixing them in specific ratios for polymerization. This forms chains that extend from a central backbone, giving the particle a bottlebrush-like structure with inactivated drugs, or prodrugs, along the bottlebrush backbone. This allows for the release of the active agent. By using this method, the researchers can create bottlebrush particles with different numbers of drugs, while maintaining the same size and shape.
In the study, the researchers tested particles carrying one drug, bortezomib, which is used to treat multiple myeloma. They found that the particles accumulated mainly in plasma cells, and protected the drug from being released prematurely, allowing it to reach its target. MIT researchers have been working on developing nanoparticles that can deliver multiple cancer drugs at once. These particles, called "bottlebrush" particles, are made by binding drug molecules to polymer building blocks and then mixing them in a specific ratio for polymerization.
This creates chains that extend from a central backbone, giving the particle a bottlebrush-like structure with inactivated drugs (prodrugs) along the bottlebrush backbone. Cleavage of the linker that holds the drug to the backbone releases the active agent. This allows the drugs to accumulate at the tumor site and reduces toxic side effects because the particles protect the drugs from being released prematurely.
MIT chemists designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled.
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Optimizing Cancer Drug Combination
By using these bottlebrush particles, the researchers were able to analyze many different drug combinations to evaluate which were the most effective, making it easier to deliver synergistic ratios to the cancer cells. However, the researchers advise that when developing a synergistic drug combination that you ultimately plan to administer in a nanoparticle, you should measure synergy in the context of the nanoparticle, because measuring it for the drugs alone cannot guarantee it will be as effective.
The researchers have found that using bottlebrush particles to deliver a combination of drugs to cancer cells can be more effective than using the drugs alone. By delivering all three drugs together in one particle, the researchers were able to overcome the obstacle of drugs being distributed and absorbed differently inside the human body, which often hinders the translation of identified synergistic drug ratios, as reported by Gene NG News.
They tested the three-drug bottlebrushes with a synergistic ratio on two mouse models of multiple myeloma and found that they significantly inhibited tumor growth compared to the free drugs given at the same ratio and to mixtures of three different single-drug bottlebrushes. The researchers have founded a company called Window Therapeutics, which is working on further developing these particles for testing in clinical trials and exploring other drug combinations that could be used against other types of cancer.
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