Drug delivery nanoparticles (stained red) are taken up by cancer cells grown in the lab. Image: Stephen Morton
In the last few years, scientists have developed a whole range of nanoparticles and complementary activation mechanisms that safely ferry and release therapeutic payloads at target sites within the body. Yet, smarter nanoparticles are on the way that can be programmed to do things in more complicated and effective ways. Researchers at MIT have reported on a new nanoparticle that can release two different drugs at different times, significantly compounding the killing effect when compared to unregulated release of the drugs.
The nanoparticle contains the cancer drug doxorubicin (green spheres) in its core. Erlotinib is embedded in the red outer shell. Attached to the surface are chains of polyethylene glycol (PEG), in yellow. Image: Stephen Morton
The liposome nanoparticle has doxorubicin at its core and erlotinib closer to the surface, two cancer drugs that are currently in clinical use. The surface was covered with a layer of polyethylene glycol (PEG) which protects the nanoparticle from being broken down and filtered out by the body. Yet, once the particle enters a tumor, it begins to break down, first releasing erlotinib and then doxorubicin some hours later. This provides an effective synergistic therapeutic effect, weakening the tumor with one compound and dealing a final blow with the other.
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The researchers tested the particles in mice implanted with two types of human tumors: triple-negative breast tumors and non-small-cell lung tumors. Both types shrank significantly. Furthermore, packaging the two drugs in liposome nanoparticles made them much more effective than the traditional forms of the drugs, even when those drugs were given in a time-staggered order.
As a next step before possible clinical trials in human patients, the researchers are now testing the particles in mice that are genetically programmed to develop tumors on their own, instead of having human tumor cells implanted in them.
The researchers believe that time-staggered delivery could also improve other types of chemotherapy. They have devised several combinations involving cisplatin, a commonly used DNA-damaging drug, and are working on other combinations to treat prostate, head and neck, and ovarian cancers.
