Drug docks onto sugar receptors
In the scientific journal "Nature Communications", the team now describes how the active substance RCS-21 is delivered to its target particularly effective via an inhaler. To do this, the researchers took advantage of a special feature of macrophages. These scavenger cells are also present in large numbers in the healthy lung. There, they perform the important task of destroying bacteria and fungal spores as quickly as possible. The macrophages identify their targets among other things based on complex sugar molecules on the surface of the invaders. "We have determined in single cell analyses that the corresponding sugar receptors are, on the one hand, among the most common receptors on macrophages," says Stefan Engelhardt. "On the other hand, the receptors are, in a sense, a unique feature of macrophages – they hardly occur anywhere else."
Therefore team coupled its active ingredient to a sugar molecule, or more precisely: to trimannose. This approach had so far only been pursued with chemically less complex active ingredients. Studies with mice produced clear results. "When the drug was administered as a spray, macrophages took up the active ingredient significantly better than without sugar molecules. In contrast, other cell types even outright exclude the molecules," says Christina Beck, first author of the article together with Deepak Ramanujam.