Cells use the messenger RNA (mRNA) to generate proteins, which help to keep the cell growing. Once the siRNA enters the cell, it binds to the mRNA and recruits proteins that attack the siRNA-mRNA complex. But the cancer cell's not finished; it keeps generating proteins, so without a continuous supply of siRNA, the cell recovers. Using the hydrogel to slowly release the siRNA allows it to keep up a sustained attack so that it can continue to interrupt the production of proteins.
"We've shown that you can get knock down out to a few days time frame, which could present a clinical window to come in and do multiple treatments in a combination chemotherapy approach," said Lyon.
"The fact that this system is releasing the siRNA slowly, without giving the cell time to immediately recover, gives us much better efficiency at killing the cancer cells with chemotherapy," added McDonald.
Previous techniques have involved using antibodies to knock down the proteins.
"But oftentimes, a mutation may arise in the targeted gene such that the antibody will no longer have the effect it once did, thereby increasing the chance for recurrence," said McDonald.
The team used hydrogels because they're non-toxic, have a relatively slow release rate, and can survive in the body long enough to reach their target.
"It's a well-defined architecture that you're using the intrinsic porosity of that material to load things into, and since our particles are about 98 percent water by volume, there's plenty of internal volume in which to load things," said Lyon.
Currently, the tests have been shown to work in vitro, but the team will be initiating tests in vivo shortly.
|Contact: David Terraso|
Georgia Institute of Technology