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    A seemingly ingenuous idea might just turn a ruthless killer into a saviour. One of the most deadly viruses known to mankind may soon help brain cancer patients. The rabies virus, which kills tens of thousands of people a year, possesses a rare knack of infecting the nerve cells and could thus be used as a conduit to infect brain tissue.

    The rabies virus generally is transmitted to humans through the bites of infected animals. Upon infection, the virus hijacks the nerve cells and ascends from the infected muscles to reach the brain. Once symptoms appear, the result is nearly always death. This unique ability of the virus that gives is access to the central nervous system (CNS) helps it bypass the blood brain barrier – a major hurdle that keeps pathogens and even drugs from entering the brain. As a result, treatment options for brain specific diseases are limited.

    Rabies virus - belongs to the lyssavirus family - causes a fatal neuroinflammatory disease in humans other mammals by specifically targeting the nerve cells
    Rabies virus – belongs to the lyssavirus family – causes a fatal neuroinflammatory disease in humans other mammals by specifically targeting the nerve cells. Image courtesy : Wikimedia Commons

    Using the virus as inspiration, scientists are trying to mimic this strategy to ship tumor-killing nanoparticles into brain tumors. They successfully packaged cancer-fighting drugs into customized nanoparticles coated with virus’ surface protein. This protein has been found to let the virus slip into the CNS. However, this approach has been found to work only in mice so far.

    Thereafter, a team of researchers from Sungkyunkwan University in Suwon, South Korea, decided to take things up a notch. Yu Seok Youn, a nanoparticle expert and his team have designed gold particles so that they have the same rodlike shape and size as the virus.  The particles don’t carry any drugs, but the tiny gold rods readily absorb laser light, which heats them up and kills surrounding tissue. The shape of the nanoparticle allows it to bind effectively with nerve cell receptors.

    Rabies virus - belonging to the lyssavirus family - causes a fatal neuroinflammatroy disease in humans and other mammals. Image Courtesy : Wikimedia Commons
    Electron micrograph of rabies virus. Gold nanoparticles were engineered that were similar to rabies virus in size and shape. Image Courtesy : Wikimedia Commons

    The next step was to test the efficacy of these nanoparticles against tumors. Youn and his team induced tumors in the mice brain and injected the particles into the tail veins of these mice. The nanoparticles quickly traveled to the brain, where they accumulated near the tumor sites. The team then fired a near infrared laser at the nanoparticles, heating them to nearly 50°C. The light harmlessly passed through skin and bone, but heat from the gold particles radiated outward, effectively cooking nearby cancer cells.

    The treatment greatly reduced the size of the tumors, Youn and his colleagues report this month in Advanced Materials. The researchers were able to reproduce this observation in another tumor model where the cells were injected in mice flanks. Tumors on two of the mice disappeared after 7 days, whereas the other tumors shrank to about half their original size.

    The team is uncertain regarding how the nanoparticles reached the tumor cells. Youn says they likely traveled the same path as the rabies virus—through the central nervous system.

    It is of great interest that these nanorods not only resembled the appearance of the live rabies virus but targeted the brain through the neuronal pathway bypassing the blood–brain barrier.

    This study, however, is also marred with a series of concerns. Rachael Sirianni, a drug delivery scientist at the Barrow Neurological Institute in Phoenix, questions quite legitimately whether the nanoparticles actually made it inside the tumor cells. It normally takes a long time for the rabies virus to traverse the central nervous system, whereas Youn’s nanoparticles made it to tumor cells in a matter of hours. They could still be effective at suppressing tumors, but they might lead to other, unwanted side effects.

    “The ideal scenario is [that] only the tumor cells take up these gold nanorods,” Sirianni says. “In reality … you’re probably getting these rods to vascular cells, between vascular cells, and [only] some of them to the tumor.” Leakage outside the tumor cells would mean that the heated particles could potentially fry healthy cells in the process.

    Another worry, according to Feng Chen, a materials scientist at the Memorial Sloan Kettering Cancer Center in New York City, is toxicity. Large nanoparticles like these often end up in the liver and take a long time to clear out. That could make it more challenging to get the therapy ready for human trials and Food and Drug Administration approval, Chen says.

    Youn is unlikely to get bogged down and is extremely optimistic. According to him, the new nanoparticles accumulate preferentially in tumors, which could drastically reduce the side effects of current cancer treatments that usually kill healthy cells along with the targeted cancer cells. He also postulates that nanoparticles are good candidates for treating other cancers located en route to the brain.

    “Researchers need to develop … nanoparticles, precisely and effectively to target tumors,” he says. “That’s my obligation.”

     

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