Could a Technique Echoing an Ancient Greek Military Strategy Point the Way to More Effective Cancer Treatments?

Trojan horse

According to Greek legend, the Trojan horse was a wooden structure built by Greek soldiers and presented to the Trojans as a gift after a long and fruitless siege of the city during the Trojan War. When the Trojans brought the gift horse within their city walls, the Greek soldiers who were hidden inside crept out under the cover of night and launched a deadly surprise attack. Historians continue to debate how much of the tale is based in fact and how much in myth.

At Massachusetts General Hospital, a real-life Trojan horse scenario that takes place on the nanoscale level could provide a way to sneak cancer drugs into fortified tumor cells so the drugs can attack from within.

Here are five things to know about a new study from the Mass General Center for Systems Biology:

    1. 1. Think of nanoparticles as the Trojan horses of cancer therapy. These tiny molecules (typically between 20 and 100 nanometers in size) are increasingly being used to transport drugs to a specific target in the body. The ability that researchers have to easily change the size and surface characteristics of the nanoparticles and control the time and location of the drug’s release makes them ideal for drug delivery systems.
    1. 2. Nanoparticles are small enough to carry the drugs (the Greek soldiers) through the body and can protect the encapsulated drug from toxic substances in the bloodstream that are used in infusion chemotherapy. However, in clinical practice, getting these nanoencapsulated drugs into patients’ tumors has been challenging—tumor blood vessels are difficult to break through, which limits the passage of any drugs from the bloodstream into tumor cells. Although it’s usually beneficial for blood vessels to maintain barrier function, their tough exteriors are a disadvantage in cancer therapies.
    1. 3. A 2015 study by Miles Miller, PhD, of the Center for Systems Biology, and his colleagues showed that tumor-associated macrophages — immune cells found around tumors that are in charge of engulfing pathogens, foreign materials and dead cells — can improve delivery of nanoparticle-based therapies to tumor cells. They also found that radiation therapy made it easier for substances to pass through tumor blood vessels. But exactly how these effects are produced and how they could be combined to enhance nanomedicine delivery was not known. Answering those questions was the goal of the current study.
    1. 4. Miller and his team found that macrophages can be prompted to act like Trojans, helping to bring the drugs inside the tumor, if the tumors are treated with radiation prior to administering the drugs. In the same way that a siege weakens the resistance of a city, the radiation weakens the blood vessels within the tumor. It also increases the number of macrophages attracted to tumor blood vessels which, in turn, pick up the drug-laden nanoparticles and bring them into the tumor. The sudden influx of macrophages into the weakened walls of the blood vessels causes many of the vessels to burst, thus flooding the tumor cells with the drug-laden nanoparticles and improving drug delivery by 600 percent.
    1. 5. “Finding that this combination of radiation and nanomedicine leads to synergistic tumor eradication in the laboratory provides motivation for clinical trials that combine tumor rewiring using radiation therapy with nanomedicine,” says Miller, who was lead author of the study. “Most of the treatments and nanomedicines employed in this study are FDA approved for cancer treatment, so this combination treatment strategy could be tested in clinical trials relatively quickly.”

     

    Radiation & Macrophages

  1. Ralph Weissleder, MD, PhD, Director of the MGH Center for Systems Biology is senior author of the Science Translational Medicine paper.

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