The nanoparticles are iron oxide spheres bound to tumor-targeting peptides and strands of DNA. The DNA is in turn bound to drugs such as cisplatin, a chemotherapy agent. When the iron oxide cores are heated up by the radio frequency waves (which don’t affect the body’s tissues), the DNA “melts”: the strands of the double helix separate, freeing the drug.
The temperature at which a strand of DNA melts depends on the strand’s length, making the nanoparticles even more versatile. Doctors could administer a cocktail of particles designed to release their drugs at different temperatures, then sequentially activate multiple doses by applying different radio frequencies. What’s more, “the patient wouldn’t have to come in for imaging, then chemotherapy, then repeated scans,” says Bhatia. Because the iron oxide doubles as a contrast agent, MRI scans administered at the time of treatment would be able to verify that a drug had reached the tumor it was targeting.
Other groups are also working on using nanoparticles for targeted chemotherapy. But either their techniques are passive–drug release cannot be controlled but happens over time–or they haven’t worked very well. Bhatia, however, demonstrated her remote-controlled nanoparticles in mice that had model tumors made of gel implanted in them. Radio frequencies applied from outside the mice triggered the release of model drugs that penetrated surrounding tissue.
Bhatia has been working on these nanoparticles for years, in collaboration with Erkki Ruoslahti, a biology professor at the University of California, Santa Barbara, who is an expert on the tumor environment, and with Michael Sailor, a chemistry professor at the University of California, San Diego.
Now, working with MIT Institute Professor Phillip Sharp, she hopes to use the particles to deliver RNA interference therapies, which show great promise but have yet to live up to their potential. In RNA interference, specially designed sequences of RNA hinder the expression of particular genes. Companies such as Alnylam hope to harness the process to therapeutically shut down disease genes, but delivery remains “a critically important problem to solve,” says Sharp, a Nobel Prize-winning biologist and a cofounder of Alnylam. In the technique Bhatia is working on, the nanoparticles would be bound to strands of RNA instead of DNA; rather than carrying a drug, she explains, the RNA would itself be the drug.
Bhatia says the great benefit of her nanoparticles is that they could “integrate detection and therapy.” Doctors treating diabetes and heart disease can already implant glucose pumps and defibrillators that don’t just administer treatment but monitor results, adjusting treatment as necessary. Similarly, Bhatia hopes, the nanoparticles will allow doctors to more quickly assess whether chemotherapy is working and modify it if it isn’t–relieving stress and saving lives.
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