TRAIL-conjugated liposomes that bind natural killer cells to induce colorectal cancer cell apoptosis.

Natural killer (NK) cell functionality is a strong indicator of favorable prognosis in cancer patients, making NK cells an appealing therapeutic target to prevent lymph node dissemination. We engineered liposomes that are conjugated with anti-CD335 antibodies for NK cell targeting, and the apoptotic ligand TRAIL to kill cancer cells. Liposomes were made using a thin film hydration method followed by extrusion to approximately 100 nm in diameter and conjugation of proteins via thiol-maleimide click chemistry. TRAIL/anti-CD335 liposomes successfully bound to isolated NK cells. Once piggybacked to the surface of NK cells, these "Super Natural Killer Cells" were able to more effectively kill oxaliplatin-resistant SW620 cells and metastatic COLO205 colorectal cancer cells via TRAIL-mediated apoptosis compared to NK cells alone. Importantly, Super NK cells were more effective under physiological levels of fluid shear stress found in the lymphatics. Liposome biodistribution after intravenous administration confirmed the sustained presence of liposomes within the spleen and tumor draining mesenteric lymph nodes for at least 4 days. These results demonstrate the enhanced apoptotic effects of NK cells armored with liposomal TRAIL against clinically relevant colorectal cancer cells, providing the groundwork for in vivo treatment studies in mouse models of colorectal cancer metastasis.