Achieving high target cell avidity in combination with cell selectivity are fundamental, but largely unachieved goals in the development of biomedical nanoparticle systems, which are intricately linked to the quantity of targeting functionalities on their surface. Viruses, regarded as almost ideal role model for nanoparticle design, are evolutionary optimized, so that they cope with this challenge bearing an extremely low number of spikes, and thus binding domains, on their surface. In comparison, nanoparticles are usually equipped with more than an order of magnitude more ligands. It is therefore obvious that one key to increasing nanoparticle efficiency in terms of avidity and selectivity lies in optimizing their ligand number. A first step along this way is to know how many ligands per nanoparticle are involved in specific binding with target cell receptors. This question is addressed experimentally for a block copolymer nanoparticle model system. The data confirm that only a fraction of the nanoparticle ligands is involved in the binding processes: With a total ligand valency of 29 ligands/ 100 nm2 surface area a maximum 5.3 ligands/ 100 nm2 are involved in specific receptor binding. This corresponds to an average number of 251 binding ligands per nanoparticle, a number that can be rationalized within the biological context of the model system.
