Platelet Membrane-Coated Nanoparticles Kill Circulating Tumor Cells and Prevent Metastasis in Breast Cancer Model

Silica nanoparticles functionalized with activated platelet membranes along with surface conjugation of the tumor-specific apoptosis-inducing ligand cytokine TRAIL were shown to facilitate the destruction of circulating tumor cells (CTCs) and prevent the spread of the disease in a mouse breast cancer metastasis model.

Investigators at Cornell University (Ithaca, NY, USA) had shown in previous studies that (CTCs) became part of a "microenvironment" when they became physically associated with activated platelets and fibrin while being transported in the bloodstream.

To attack the tumor cells within this microenvironment, the investigators prepared synthetic silica nanoparticles coated with proteins from activated platelet membranes. Molecules of the cytokine TRAIL (tumor necrosis factor related apoptosis-inducing ligand) were attached to the surface of the particles.

TRAIL is a cytokine that is produced and secreted by most normal tissue cells. It causes apoptosis primarily in tumor cells by binding to certain death receptors. Since the mid-1990s it has been used as the basis for several anti-cancer drugs, but had not been found to have any significant survival benefit.

The investigators reported in the October 21, 2015, online edition of the journal Biomaterials that their synthetic nanoparticles attached to "natural killer cells" in the blood which then became incorporated into CTC-associated micro-thrombi in blood vessels within the lungs. The ramped-up killer cells acted to dramatically decrease lung metastases in a mouse breast cancer metastasis model.

"In our research, we use nanoparticles— the liposomes we have created with TRAIL protein—and attach them to natural killer cells, to create what we call "super natural killer cells" and then these completely eliminate lymph node metastases in mice," said senior author Dr. Michael R. King, professor of biomedical engineering at Cornell University. "So, now we have technology to eliminate bloodstream metastasis—our previous work—and also lymph node metastases."

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