image: This is a schematic illustration of selectins' role in inflammation (A) and cancer progression (B). This mechanism can be used for selectin-based targeted therapy (C). This material relates to a paper that appeared in the June 29, 2016 issue of <i>Science Translational Medicine</i>, published by AAAS. The paper, by Y. Shamay at Memorial Sloan Kettering Cancer Center in New York, NY, and colleagues was titled, "P-selectin is a nanotherapeutic delivery target in the tumor microenvironment." view more
Credit: Kedmi <i>et al., Science Translational Medicine</i> (2016)
Zap a tumor with radiation to trigger expression of a molecule, then attack that molecule with a drug-loaded nanoparticle. That's the approach researchers working in mice have taken in a new study that aims to make delivery of chemotherapy to metastatic tumors more effective. The researchers say that the radiation-guided nanoparticles may offer a new approach for penetrating the vascular barrier that often thwarts current nanomedicines from reaching metastatic tumors. To spread to distant organs, cancer cells in the bloodstream latch onto adhesion molecules known as P-selectins in the blood vessel walls. Yosi Shamay and colleagues further found that unlike normal tissues, many human cancers--including lung, ovarian, breast, and liver--overexpress P-selectin on tumor cells and in surrounding blood vessels. To exploit this molecule as a therapeutic target, the researchers designed nanoparticle drug carriers composed of fucoidan, a seaweed-derived compound that naturally binds to P-selectin. In a mouse model of lung cancer and metastatic melanoma and breast tumors, all of which express P-selectin, the nanoparticles selectively delivered chemotherapy drugs to the tumors, improving tumor reduction and overall survival better than did the free form of the drugs or drug-loaded nanoparticles not made of fucoidan. For tumors that do not normally express P-selectin, Shamay et al. used radiation, which is known to boost P-selectin expression in tissues, to guide the nanoparticles to the tumor site. When combined with radiation, the nanotherapy effectively shrunk lung tumors lacking P-selectin in mice. In a related Focus, Ranit Kedmi and Dan Peer discuss the promises and challenges of moving the nanotherapy to the clinic. Radiation-guided nanoparticles may offer a new tool for delivering drugs to almost any tumor, they note, but further development would need to address the double-edged sword of radiation's potential to trigger P-selectin expression that might unintentionally promote cancer spread.
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Journal
Science Translational Medicine