- Challenges and Perspectives in Polyelectrolytes.

Polyelectrolytes offer unique properties for biological applications due to their charged nature and high water solubility. Here, the challenges in their synthesis and characterization techniques are reviewed, emphasizing that their strong interactions with the surrounding media and counterions must be considered when working with this interesting class of materials. Their potential in complexation for gene delivery, their unique stealth and anti-fouling properties, and their more specific interactions with amino acid transporters for cancer therapy are highlighted. The underlying mechanisms responsible for their biological efficacy, including the proton sponge effect for endosomal release and their interactions with cellular membranes, are addressed. For polyelectrolytes with a high level of usage, an overview is given of their historical context. This Perspective outlines the potential of polyelectrolytes for innovative applications in the field of biomedicine. Considering the physicochemical characteristics of this class of materials, this work strives to elucidate the distinctive properties and applications of polyelectrolytes.