Dynamic Self-Assembly of Polycationic Clusters Based on Cyclodextrins for pH-Sensitive DNA Nanocondensation and Delivery by Component Design

The ability of cyclodextrin‐based polycationic cluster to undergo reversible DNA condensation and release in a physiologically useful pH window has been finely tuned by the installation of a capping xylylene moiety at the secondary face of the cyclooligosaccharide. This strategy can be exploited advantageously in the design of self‐assembling nonviral gene‐delivery systems from molecular entities. Programming self‐assembly: pH‐Sensitive, hierarchical self‐assembly of cyclodextrin‐based polycationic clusters and DNA was programmed by the installation of a xylylene moiety at the secondary face of the cyclooligosaccharide. At neutral pH dimer formation facilitates DNA condensation, whereas at acidic pH electrostatic repulsions promote disassembly of the nanocomplexes and DNA release. This can be exploited advantageously in the design of nonviral gene delivery systems (see figure).