MIT chemists have now shown, they can package three or more drugs into a novel type of nanoparticle, allowing them to design custom combination therapies for cancer. In tests in mice, the researchers showed, the particles could successfully deliver three chemotherapy drugs and shrink tumours.
The study, which appeared in the latest issue of Journal of the American Chemical Society, showed, when drugs are delivered by nanoparticles, it don?t necessarily work by the same DNA-damaging mechanism, as in its traditional form.
The new nanoparticle production technique, which Johnson?s lab first reported in 2014 differs from other methods that encapsulate drugs or chemically attached them to a particle. Instead, the MIT team creates particles from building blocks that already contain drug molecules. They can join the building blocks together in specific structure and precisely control how much of each drug is incorporated.
?We can take any drug, as long as it has a functional group - a group of atoms that allows a molecule to participate in chemical reactions, and we can load it into our particles in exactly the ratio that we want, and have it release under exactly the conditions that we want it to,? said Jeremiah Johnson, the Firmenich Career Development Associate Professor of Chemistry and the senior author of the paper. ?It?s very modular.?
A key advantage is that this approach can be used to deliver drugs that normally can?t be encapsulated by traditional methods.
Using the new particles, the researchers delivered doses of three chemotherapy drugs ? cisplatin, doxorubicin, and camptothecin ? at concentrations that would be toxic if delivered by injection throughout the body, as chemotherapy drugs usually are. In mice that received this treatment, ovarian tumours shrank and the mice survived much longer than untreated mice, with few side effects.
Using a method developed by Hemann?s lab, the researchers then investigated how their nanoparticle drugs affect cells. The technique measures cancer drugs? effects on more than 100 genes that are involved in the programmed cell death often triggered by cancer drugs. This allows scientists to classify the drugs based on which clusters of genes they affect.
?Drugs that damage DNA get clustered into DNA damage-inducing agents, and drugs that inhibit topoisomerases cluster together in another region,? Johnson says. ?If you have a drug that you don?t know the mechanism of, you can do this test and see if the drug clusters with other drugs whose actions are known. That lets you make a hypothesis about what the unknown drug is doing.?
The team is also developing nanoparticles with different combinations of drugs to test against pancreatic and other types of cancers.