December 22, 2009 - Researchers at Rice university and Baylor College of Medicine have created a nanoparticle trackable with MRIs that locates cancer cells, tags them with a fluorescent dye, and kills them with heat -- a first example of "thernostic," or essentially patient-customized, medical treatment.
Their work, published in the Nov. 17 issue of Advanced Functional Materials, centers on the idea of noninvasive "biodistribution," i.e., how and where tiny particles go inside the body. The particles involved are based on "nanoshells," structures invented in the 1990s and currently being used in human clinical trials for cancer treatment; these structures harvest light that would otherwise pass harmlessly through the body, and convert it into heat to attack and kill tumors. The teams from Rice and Baylor added a fluorescent dye to these nanoshells to make them glow when struck by near-infrared light. Leaving a few-nanometer-wide gap between the dye molecules and nanoshell surface increased light emission by 40×50× they note; in this gap they inserted an iron oxide, detectable with MRI; they also attached an antibody to help the particles bind to breast and ovarian cancer cells. The team tracked the nanoparticles, confirming that they target cancer cells and then destroy them with heat.
Breast cancer cells after treatment with light-activated, antibody-containing nanocomplexes, which specifically target the cells; upon laser activation they convert light to heat and kill the cancer cells. Dead cells are shown in red within the area where laser was applied (white circle), and live cells are shown in green. (Source: Rice U.)
"What's nice is that every single component of this has been approved or is on a path toward FDA approval," stated study co-author Naomi Halas, Rice prof. in electrical and computer engineering and prof. of chemistry and biomedical engineering. "We're putting together components that all have good, proven track records." And with four options (two for imaging, two for therapy), "we envision this as a platform technology that will present practitioners with a choice of options for directed treatment," added Amit Joshi, assistant professor in the Baylor College of Medicine's division of molecular imaging.
From the paper abstract:
Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously - fluorescence optical imaging and magnetic resonance imaging - with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell-based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe3O4 and the fluorophore ICG, which results in a high T2 relaxivity (390 mM-1 s-1) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near-IR illumination.
Tests so far involve lab cell cultures, but the researchers are optimistic that MRI tracking will help them move the work ahead to testing on whole tumors in animals. Testing on humans is said to be at least two years away, though the researchers already envision how it would work: a patient gets a shot containing nanoparticles with antibodies tailored for that patient's specific cancer; using near-infrared light or MRI, doctors track the particles until they hit the tumors and then destroy them with heat. Ultimately, specific versions of the nanoparticles could target tumors with different stages (e.g. early-stage which is difficult to diagnose and treat), and use different antibody labels to treat different forms of the disease.