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Radiation Enhances Nanoparticle Cancer Treatments

Cancer in headline


30 June 2016. A strategy targeting vulnerable proteins on tumors with chemotherapy delivered in nanoscale particles and preceded with shots of radiation was shown in lab mice to boost treatment effectiveness in a range of cancers. A team from the lab of Daniel Heller at Memorial Sloan Kettering Cancer Center in New York published its findings in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

Heller’s lab studies the use of nanoscale drug delivery technologies — 1 nanometer equals 1 billionth of a meter — for treating metastatic cancer that spreads from original cancer sites and is responsible for 90 percent of cancer deaths. Delivering cancer drugs in nanoscale pieces makes it possible to target tumors directly, preventing drugs from building up and harming healthy tissue, a major problem encountered with many current cancer treatments.

Delivering drugs as nanoparticles, however, encounters problems with extravasation, or leakage into tissue surrounding the tumor site. To overcome this problem, Heller and colleagues designed a technique that aims nanoparticles with chemotherapy drugs directly at a protein called P-selectin found in blood platelets and cells lining blood vessels, as well as expressed on some metastatic tumor cells, including lung, ovarian, breast, and liver. The nanoparticles are made of fucoidan, a natural carbohydrate material derived from seaweed, and known to attract and bind to P-selectin.

The researchers tested fucoidan nanoparticles delivering chemotherapy drugs paclitaxel and doxorubicin with lab mice induced with melanoma, an advanced and aggressive form of skin cancer, and breast cancer. Results were compared to similar tumors on mice treated with nanoparticles made with dextran sulfate, a sodium salt compound used frequently as a stabilizer, and chemotherapy drugs delivered in free form. The results show mice receiving the fucoidan nanoparticles had greater tumor reduction and longer survival than mice receiving dextran sulfate nanoparticles or chemotherapy in free form.

While P-selectin is found on a number tumor cells, not all tumors express this protein target. The researchers also tested radiation as a way to make tumors that do not express P-selectin on their surface more vulnerable to fucoidan nanoparticles. The team grafted on the hind limbs of lab mice a form of lung cancer without P-selectin, and subjected one of the limbs to X-ray doses. The results show the tumors on the limb receiving X-rays started expressing P-selectin in about 4 hours, and increased over 24 hours.

In addition, the team found the tumor on the limb not receiving X-rays also expressing P-selectin proteins about 24 hours after the radiation, a phenomenon known as abscopal effect. Tests of fucoidan nanoparticle treatments in lab mice with tumors receiving X-rays show more chemotherapy drugs delivered to the tumor sites, as well as less tumor growth, and in some cases complete tumor regression.

The authors say this process still needs further refinement, particularly when dealing with radiation that can be toxic in some cases. Nonetheless, Heller and first author Yosi Shamay filed a patent for the targeted nanoparticle technology.

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