Zwitterionic supramolecular nanoparticles: Self-assembly and responsive properties

Supramolecular nanoparticles (SNPs) are of high interest in both nanoscience and molecular diagnostics and therapeutics, because of their reversible and designable properties. To ensure colloidal stabilization and biocompatibility, most reported strategies require the use of hydrophilic long-chain polymers such as poly(ethylene glycol). Here, we show the formation of zwitterionic supramolecular nanoparticles (ZSNPs) from appropriately functionalized mono- and multivalent components, based on the hetero-ternary host-guest complexation between cucurbit[8]uril (CB[8]), methyl viologen (MV), and azobenzene (Azo), while using the monovalent, small-molecule, non-fouling Azo-carboxybetaine analog (Azo-Zwit) as the shell-forming component. Even though steric shell stabilization is absent, the zwitterionic Azo-Zwit ensures stability of the ZSNPs in water, in PBS (pH 7.4) at ionic strengths ranging from 0-700 mM, and in PBS containing BSA. Size tuning by control over the stoichiometry of the components, as well as reversible assembly and disassembly by photoisomerization of the Azo moieties were observed. Surprisingly, the ZSNPs exhibited aggregation at the narrow pH range of 6.2-6.8.