Exploring ‘new’ bioactivities of polymers at the nano–bio interface

•Beyond their traditional roles, polymers can directly serve as therapeutic agents.•Polymers gain new bioactivities when they interact with the biological system.•Their size must be sufficiently large to form nanostructures with other molecules.•Polymers may gain new activities only in vivo, based on the formation of a ‘corona’.

A biological system is essentially an elegant assembly of polymeric nanostructures. The polymers in the body, biomacromolecules, are both building blocks and versatile messengers. We propose that non-biologically derived polymers can be potential therapeutic candidates with unique advantages. Emerging findings about polycations, polysaccharides, immobilised multivalent ligands, and biomolecular coronas provide evidence that polymers are activated at the nano–bio interface, while emphasising the current theoretical and practical challenges. Our increasing understanding of the nano–bio interface and evolving approaches to establish the therapeutic potential of polymers enable the development of polymer drugs with high specificities for broad applications.