We discovered that when the nanoparticle binds to P-selectin, it triggers a process called transcytosis, a mechanism that shuttles a particle across the cells lining the blood vessel wall. The blood vessels in the blood-brain barrier are lined with a layer of cells that are packed very close together. How does targeting P-selectin get drugs across the blood-brain barrier? This showed the promise of targeting P-selectin to treat cancer. In the 2016 study, we filled fucoidan nanoparticles with different cancer drugs and showed that the nanoparticles selectively attached to cancer sites, including metastatic tumors in the lungs of mice. It’s called fucoidan, a polysaccharide (a chain of sugar molecules) that is widely available and extracted from brown seaweed from the Sea of Japan. We found a substance that has a natural affinity for P-selectin.

P-selectin is abundant in blood vessels that feed tumors. In 2016, my laboratory found that a protein called P-selectin is an especially good target on cancer blood vessels for steering nanoparticles, loaded with drugs, to tumors. How are nanoparticles used to target tumors across the blood-brain barrier? Heller explains how this method, reported March 2 in Nature Materials, could potentially improve treatment for medulloblastoma, other brain tumors, and other brain diseases.

The researchers showed that this approach could work in mouse models of medulloblastoma, the most common malignant (cancerous) pediatric brain tumor. Now, a Memorial Sloan Kettering Cancer Center (MSK) team led by Sloan Kettering Institute biomedical engineer Daniel Heller, PhD, in collaboration with Praveen Raju, MD, PhD, a pediatric neurologist at Mount Sinai Medical Center, may have found a way to carry drugs across the blood-brain barrier using nanoparticles - tiny objects with diameters one-thousandth that of a human hair.

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