Spiky particles enhance immune responses in mice

Vaccines and cancer immunotherapies work by activating the immune system with biochemical signals. A new study shows that the immune system can also respond to physical cues such as the texture of injected nanoparticles, potentially opening up new ways to design therapies for cancer and other diseases.

Many pathogens, including the flu virus, have spikelike features on their surface, and scientists have wondered whether their characteristic shapes have a role in triggering the immune system. To test whether physical cues could help activate an immune response, Mei X. Wu of Massachusetts General Hospital and Xi Xie of Sun Yat-Sen University designed an experiment that allowed them to isolate shape-based and biochemical cues.

First, they made two sets of nanoparticles from titanium dioxide, a compound that doesn’t usually trigger the immune system. Some were spiky, some rough. They coated some of them with a lipid found on the surface of some bacterial cells to act as an immune irritant. Then they injected mice with the particles along with a cancer therapy and a flu vaccine. The lipid-coated spiky particles amplified immune responses and boosted the efficacy of cancer immunotherapy and the flu vaccine in mice. Coated rough particles had no significant effect (Nat. Nanotech. 2018, DOI:10.1038/s41565-018-0274-0).

Cells dosed with spiky particles showed evidence of mechanical stress on their membranes, and activation of a signaling pathway known to play a critical role in response to immunotherapies. Researchers suspect that the spikes stress the cell membrane, causing potassium channels in the cells to open and ultimately activating the pathway.

Wu says researchers designing immunotherapies should take advantage of these effects. Therapies combining physical and biochemical cues could produce more robust responses. And they could be approved quickly because the materials used in this study are already in medical use, says John Hayball of the University of South Australia.

Brandon M. Johnson of University of North Carolina, Chapel Hill, who wrote a perspective article about the study (Nat. Nanotech. 2018, DOI:10.1038/s41565-018-0292-y), says it would be interesting to see if the stiffness of the spikes makes a difference and whether other, less rigid materials such as polymers could achieve similar effects.