University of Pittsburgh researchers have designed cancer-fighting nanoparticles that co-deliver a chemotherapy drug and a novel immunotherapy, according to a new Nature Nanotechnology study published today.
Electron microscopy image of nanoparticles containing the chemotherapy drug FuOXP and novel immunotherapy of siRNA that blocks expression of Xkr8. Credit: Chen et al., 2022, Nature Nanotechnology, 10.1038/s41565-022-01266-2 The new immunotherapy approach silences a gene that the researchers discovered was involved in immunosuppression. When combined with an existing chemotherapy drug and packaged into tiny nanoparticles, the therapy shrunk tumors in mouse models of colon and pancreatic cancer. "There are two innovative aspects of our study: the discovery of a new therapeutic target and a new nanocarrier that is very effective in selective delivery of immunotherapy and chemotherapeutic drugs," said senior author Song Li, M.D., Ph.D., professor of pharmaceutical sciences in the Pitt School of Pharmacy and UPMC Hillman Cancer Center investigator. "I'm excited about this research because it's highly translational. We don't know yet whether our approach works in patients, but our findings suggest that there is a lot of potential." Chemotherapy is a pillar of cancer treatment, but residual cancer cells can persist and cause tumor relapse. This process involves a lipid called phosphatidylserine (PS), which is usually found inside the tumor cell membrane's inner layer but migrates to the cell surface in response to chemotherapy drugs. On the surface, PS acts as an immunosuppressant, protecting remaining cancer cells from the immune system. The Pitt researchers found that treatment with chemotherapy drugs fluorouracil and oxoplatin (FuOXP) led to increased levels of Xkr8, a protein that controls distribution of PS on the cell membrane. This finding suggested that blocking Xkr8 would prevent cancer cells from shunting PS to the cell surface, allowing immune cells to mop up cancer cells that lingered after chemotherapy. In an independent study that was recently published in Cell Reports, Yi-Nan Gong, Ph.D., assistant professor of immunology at Pitt, also identified…