MIT chemists design nanoparticles that can deliver three cancer drugs at a time
Create building blocks that can be joined together in a very specific structure
Delivering chemotherapy drugs in nanoparticle form could help reduce side effects by targeting the drugs directly to the tumours. Scientists have developed nanoparticles that deliver one or two chemotherapy drugs, but it has been difficult to design particles that can carry any more in a precise ratio.
Chemists at Massachusetts Institute of Technology (MIT) in the US have now devised a new way to build such nanoparticles, making it much easier to include three or more different drugs.
In a paper published in the Journal of the American Chemical Society, the researchers showed that they could load their particles with three drugs commonly used to treat ovarian cancer.
'We think it’s the first example of a nanoparticle that carries a precise ratio of three drugs and can release those drugs in response to three distinct triggering mechanisms,' said Jeremiah Johnson, an assistant professor of chemistry at MIT and the senior author of the paper.
Instead of building the particle and then attaching drug molecules, Johnson created building blocks that already include the drug
Such particles could be designed to carry even more drugs, allowing researchers to develop new treatment regimens that could kill cancer cells more effectively while avoiding the side effects of traditional chemotherapy. Johnson and his colleagues demonstrated that the triple-threat nanoparticles could kill ovarian cancer cells more effectively than particles carrying only one or two drugs, and they have begun testing the particles against tumours in animals.
Johnson’s new approach overcomes the inherent limitations of the two methods most often used to produce drug-delivering nanoparticles: encapsulating small drug molecules inside the particles or chemically attaching them to the particle. With both of these techniques, the reactions required to assemble the particles become increasingly difficult with each new drug that is added.
Combining these two approaches – encapsulating one drug inside a particle and attaching a different one to the surface – has had some success, but is still limited to two drugs.
Instead of building the particle and then attaching drug molecules, Johnson created building blocks that already include the drug. These can be joined together in a very specific structure, and the researchers can precisely control how much of each drug is included.
Each building block has three components: the drug molecule, a linking unit that can connect to other blocks, and a chain of polyethylene glycol (PEG), which helps protect the particle from being broken down in the body. Hundreds of these blocks can be linked using an approach Johnson developed called 'brush first polymerisation'.
'This is a new way to build the particles from the beginning,' Johnson said. 'If I want a particle with five drugs, I just take the five building blocks I want and have those assemble into a particle. In principle, there’s no limitation on how many drugs you can add, and the ratio of drugs carried by the particles just depends on how they are mixed together in the beginning.'
Johnson’s lab is now working on particles that carry four drugs, and the researchers are also planning to tag the particles with molecules that will allow them to home into tumour cells by interacting with proteins found on the cell surfaces.
