Combined Drug Therapy for Glioblastoma Tumors Using Nanoparticles
The current treatment strategies for glioblastoma (GBM) are limited by the presence of the blood–brain barrier (BBB) and the developing resistance to single agent therapies. In order to address this, MIT researchers have now devised a new drug-delivering nanoparticle that is capable of carrying two different drugs.
These drugs are designed so as to easily cross the blood-brain barrier and bind directly to cancerous cells. Both drugs have unique functions- while one damages the tumor cells’ DNA, while the other interferes with the systems cells normally use to repair such damage.
“What is unique here is we are not only able to use this mechanism to get across the blood-brain barrier and target tumors very effectively, we are using it to deliver this unique drug combination,” says Paula Hammond, a David H. Koch Professor in Engineering, the head of MIT’s Department of Chemical Engineering, and a member of MIT’s Koch Institute for Integrative Cancer Research.
The researchers based their investigation on past work by Scott Floyd and Michael Yaffe- loading the nanoparticle’s heart with temozolomide and adding the bromodomain inhibitor to the fatty outer shell that.
The particles are then coated in a protein
called transferrin, which hones in on and latches onto proteins at the surface of cells. This is what prevents it from attacking healthy cells also ensures the medication just hurts the glioblastoma.Since treatment is indeed targeted, higher doses of chemotherapy medications can be treated without sparking unwanted effects such as nausea and bruising.
Transferrin is what additionally enables the nanoparticles to maneuver the blood-brain barrier- the brain’s defense mechanisms, protecting it in any potentially toxic molecules lurking inside the bloodstream. Without it, the nanoparticles would not even have the ability to accomplish the tumor.
In the animal study, the investigators found that animals medicated with all the targeted nanoparticles experienced less damage to blood cells and other cells usually harmed by temozolomide.
The particles can also be coated with a polymer called polyethylene glycol (PEG), which can help shield the particles out of being discovered and broken down from the immune system. PEG and all the other elements of the liposomes are already FDA-approved to be used in people.
“Our goal was to have something that could be easily translatable, by using simple, already approved synthetic components in the liposome,” paper’s lead author is Fred Lam, a Koch Institute research scientist says. “This was really a proof-of-concept study [showing] that we can deliver novel combination therapies using a targeted nanoparticle system across the blood-brain barrier.”
“Because there’s such a short list of drugs that we can use in brain tumors, a vehicle that would allow us to use some of the more common chemotherapy regimens in brain tumors would be a real game-changer,” Scott Floyd, a former Koch Institute clinical investigator who is now an associate professor of radiation oncology at Duke University School of Medicine, says. “Maybe we could find efficacy for more standard chemotherapies if we can just get them to the right place by working around the blood-brain barrier with a tool like this.”
