MRI nanoparticles seek and destroy cancer cells

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A single nanoparticle can be tracked using real-time MRI as it homes in on cancer cells. A fluorescent dye used to tag the nanoparticle couples with heat therapy to kill the targeted cells.

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Naomi Halas and Amit Joshi of Rice University and their colleagues there and at Baylor College of Medicine (BCM), both in Houston, Texas, have demonstrated the "theranostics" approach in laboratory cell cultures so far but are confident that they will, one day, be able to use this approach to MRI tracking and cancer cell targeting in animals, then people. The all-in-one particle is another example of the growing field of theranostics being developed to allow physicians to diagnose and treat disease in a single procedure. The team reports details in the journal Advanced Functional Materials.

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"Some of the most essential questions in nanomedicine today are about biodistribution - where particles go inside the body and how they get there," explains Halas. "Non-invasive tests for biodistribution will be enormously useful on the path to approval [by the US Food & Drug Administration], and this technique - adding MRI functionality to the particle you're testing and using for therapy - is a very promising way of doing this."

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Halas is Rice's Stanley C. Moore Professor in Electrical and Computer Engineering and professor of chemistry and biomedical engineering. Her pioneering work in nanomedicine has seen the development of these all-in-one theranostic particles based on nanoshells she invented in the 1990s. The nanoshells themselves are already in human clinical trials for cancer treatment. They work by harvesting laser light that would normally pass harmlessly through the body and converting it into tumour-killing heat.

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In designing the new particle, Halas partnered with Amit Joshi, assistant professor in BCM's Division of Molecular Imaging, to modify the nanoshells by adding a fluorescent dye that glows when struck by near-infrared (NIR) light. The addition of NIR functionality offers an invisible and harmless adjunct to disease diagnostics, the team explains, that avoids surgery.

However, while finding ways to bond the NIR dye molecules to the nanoshells, graduate student, Rizia Bardhan in Halas' laboratory discovered that dye molecules could emit some 40 to 50 times more light if a tiny gap were left between them and the surface of the nanoshell. The gap is just a few nanometres across, but rather than leave empty space, Bardhan tried filling the gap with a layer of iron oxide, which would then make the nanoparticles detectable with MRI scanning. Simultaneously, the team worked on a way to attached antibodies that would allow the particles to find and bind to the surface of breast and ovarian cancer cells.

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"This particle provides four options -- two for imaging and two for therapy," Joshi said. "We envision this as a platform technology that will present practitioners with a choice of options for directed treatment."

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In laboratory tests, the team was able to track the fluorescent particles and confirm that they did indeed target only cancer cells and then estroy them with a burst of heat. The next step, adds Joshi, will be to destroy whole tumours in live animals. He estimates that testing in humans is at least two years away, but the ultimate goal would be a technique in which the patient is given an injection containing nanoparticles with antibodies that are tailored precisely for their particular strain of cancer. Using NIR imaging, MRI or a combination of the two, doctors could then observe the particles' progress through the body, identify areas where tumours exist with great precision and then use the laser light to heat to kill them, hopefully without harming healthy cells.

Joshi adds that designer versions of the nanoparticles will be possible. These could be used to home in on and attack cancer cells at different stages of development. This could be especially important for early stage cancer, which is often difficult to diagnose and treat with current technologies. Halas points out that the various components of their technology are already approved for medical use or are in clinical trials and so there should be a smoother route to final approval once the new, combined application of those technologies is tested in the clinic and provesitself efficacious.

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"What's nice is that every single component of this has been approved or is on a path toward FDA approval," Halas said. "We're putting together components that all have good, proven track records."