Researchers at MIT have developed a method of creating nanoparticles that can carry three or more different chemo drugs simultaneously into a tumor. Moreover, in an unusual twist, it seems like the drugs ended up acting differently than when delivered systemically, pointing to the delivery method affecting how a medication actually behaves. “People tend to take it as a given that when you put a drug into a nanoparticle it’s the same drug, just in a nanoparticle,” said Jeremiah Johnson, associate professor of chemistry at MIT in a statement. “Here, in collaboration with Mike Hemann [associate professor of biology], we conducted detailed characterization using an RNA interference assay that Mike developed to make sure the drug is still hitting the same target in the cell and doing everything that it would if it weren’t in a nanoparticle.”
Instead of binding drugs to custom nanoparticles or enclosing them inside some kind of vesicles, MIT’s technique works kind of like Lego blocks that contain different drug compounds and stick together thanks to a bit of novel chemical engineering. In addition to deciding which drugs to combine, the new method also lets scientists define how much of each drug should end up within final nanostructure, allowing for more targeted and more powerful therapies.
More from MIT’s announcement:
The researchers found that nanoparticle-delivered camptothecin and doxorubicin worked just as expected. However, cisplatin did not. Cisplatin normally acts by linking adjacent strands of DNA, causing damage that is nearly impossible for the cell to repair. When delivered in nanoparticle form, the researchers found that cisplatin acts more like a different platinum-based drug known as oxaliplatin. This drug also kills cells, but by a different mechanism: It binds to DNA but induces a different pattern of DNA damage.
The researchers hypothesize that after cisplatin is released from the nanoparticle, via a reaction that kicks off a group known as a carboxylate, the carboxylate group then reattaches in a way that makes the drug act more like oxaliplatin. Many other researchers attach cisplatin to nanoparticles the same way, so Johnson suspects this could be a more widespread issue.
His lab is now working on a new version of the cisplatin nanoparticle that operates according to the same mechanism as regular cisplatin. The team is also developing nanoparticles with different combinations of drugs to test against pancreatic and other types of cancers.
Study in Journal of the American Chemical Society: Using an RNAi Signature Assay To Guide the Design of Three-Drug-Conjugated Nanoparticles with Validated Mechanisms, In Vivo Efficacy, and Low Toxicity…