In a diseased liver, as in a city after a long siege, neighborhoods appear where life has frozen: instead of working cells there is scar tissue, and inside it hide senescent macrophages. These cells have stopped dividing but have not gone to rest. They release substances that make their neighbors build even more scar and drive away immune patrols. Drugs against them exist, but they act like carpet bombing: they kill both senescent and healthy cells, causing severe side effects.

Scientists have found a way to strike precisely. On the surface of harmful macrophages in fibrotic tissue of the liver and lungs there is the protein P-selectin, like an identification mark on a door. They found a key to it: fucoidan, a substance from brown algae that binds tightly to this protein. From fucoidan they made nanoparticles and loaded them with drugs that kill senescent cells or suppress their harmful secretions. The particles were administered to mice with liver or lung fibrosis. They accumulated specifically in the diseased organ, and within it in senescent macrophages with P-selectin, without touching other cells.

The result was twofold. The nanoparticles reduced scarring no worse than the free drug, yet the severe side effects disappeared: the drop in immune cells, weight loss, and death of the animals. And after the removal of senescent macrophages, immune cells returned to the tissue, and it stopped suppressing immunity. In cancer models against a background of fibrosis, the nanoparticles together with immunotherapy caused a sustained reduction in tumors and prolonged the lives of the mice, whereas without the nanoparticles the tumors did not respond to treatment. The sniper is ready; all that remains is to test it in humans.

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