Removable 'Cloak' for Nanoparticles Helps Them Target Tumors
Chemical engineers at the Massachusetts Institute of Technology have designed a new type of drug-delivery nanoparticle that exploits a trait shared by almost all tumors: They are more acidic than healthy tissues. Such particles could target nearly any type of tumor, and can be designed to carry virtually any type of drug, says Paula Hammond, a member of the MIT-Harvard Center of Cancer Nanotechnology Excellence and leader of the investigators who built these new nanoparticles. The results of their experiments were published in the journal ACS Nano.
Like most other drug-delivering nanoparticles, the new MIT particles are cloaked in a polymer layer that protects them from being degraded by the bloodstream. In this case, however, the MIT team designed that outer layer to fall off after entering the slightly more acidic environment near a tumor. Shedding that protective layers reveals another layer that is able to penetrate individual tumor cells.
The new MIT approach differs from that taken by most nanoparticle designers who typically try to target their particles to a tumor by decorating them with molecules that bind specifically to proteins found on the surface of cancer cells. The problem with that strategy is that it's difficult to find the right target, that is, a molecule found on all of the cancer cells in a particular tumor but not on healthy cells. In addition, a target that works for one type of cancer might not work for another, limiting the utility of the resulting drug. Instead, Dr. Hammond and her colleagues decided to take advantage of tumor acidity, which is a byproduct of a tumor's revved-up metabolism.
To build their targeted particles, the researchers used a technique called "layer-by-layer assembly." This means each layer can be tailored to perform a specific function. When the outer layer, made of polyethylene glycol, or PEG, breaks down in the tumor's acidic environment, a positively charged middle layer is revealed, one that helps the nanoparticle to breach the negatively charged cell membrane. The nanoparticles' innermost layer can be a polymer that carries a cancer drug, or a quantum dot that could be used for imaging, or virtually anything else that the designer might want to deliver, said Dr. Hammond. Other researchers have tried to design nanoparticles that take advantage of tumors' acidity, but Dr. Hammond's particles are the first that have been successfully tested in living animals.
This work, which is detailed in a paper titled, "Layer-by-Layer Nanoparticles with a pH-Sheddable Layer for in Vivo Targeting of Tumor Hypoxia," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site.