April 18, 2014
A Triple Threat To Cancer
A horrible truth about cancer is that the cure is often nearly as bad as the disease. Chemotherapy, though it has saved countless lives, is very hard on the body, as it is not a selective cure. It does not target only the cancer, but all of the body. This has spurred a great deal of research into more selective methods of treatment, hoping to make them gentler on the patient while still maintaining the strength of the treatment. Having seen the weakness, nausea, and vulnerability that being on chemotherapy can cause, I welcome any news about such a cure. In the past few years, there has been a lot of progress made with chemotherapy drugs being delivered by nanoparticles. These have shown great promise, as they are more selective in targeting cancerous regions of the body, but even these have a limit. Namely, they have had a limit in only being able to deliver two different drugs at once. One that is encapsulated within the nanoparticle while the other is chemically attached to the outside. Fortunately, there has recently been a breakthrough in nanoparticle science that has overcome this limitation.
Jeremiah Johnson, an assistant professor of chemistry at the Massachusetts Institute of Technology, has developed a way that any number of chemotherapy drugs can be delivered at once using nanoparticles. To illustrate this, Johnson and his team of researchers have created particles that contain the drugs cisplatin, doxorubicin, and camptothecin, all of which are often used to treat ovarian cancer. How they did this was to create the building blocks of the nanoparticles that already included the selected drugs. These blocks each contain three components. The first of these being the drug molecule, then a linking unit that is able to link up to the other blocks of different drugs, and finally a chain of polyethylene glycol (PEG), which can protect the particle from being broken down when it enters the body. These blocks are then able to be combined in any feasible way, allowing hundreds of these blocks to work in concert to provide direct and powerful treatment, using a method that Professor Johnson calls “brush first polymerization.” Each particle has the three drugs combined together into a specific ratio that meets the highest tolerated dose of each and is given its own, unique release mechanism. For this example, cisplatin is released as soon as the the particle enters a cell as its bonds break down upon exposure to glutathione, an antioxidant in cells. Then, the camptothecin is released when it is met with esterases, a cellular enzyme. Finally, doxorubicin is released only by ultraviolet light, allowing it to be further controlled by the researchers. All that is left of the particles once the drugs have been released is the PEG, which is easily absorbed by the body.
According to Johnson, “This is a new way to build the particles from the beginning. If I want a particle with five drugs, I just take the five building blocks I want and have those assembled 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.”
With the help of researchers in the lab of Paula Hammond, the David H. Koch Professor of Engineering and member of MIT’s Koch Institute for Integrative Cancer Research, the combination of sisplatin, comptothecin, and doxorubicin was tested against ovarian cancer cells that were lab grown. What they found were that these triple-threat nanoparticles were able to kill the cancer cells at a much higher rate than when they were using only the two-drug nanoparticles.
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