Supramolecular nanoparticles (SNPs) encompass multiple copies of different building blocks brought together by specific noncovalent interactions. The inherently multivalent nature of these systems allows control of their size as well as their assembly and disassembly, thus promising potential as biomedical delivery vehicles. Here, dual responsive SNPs have been based on the ternary host-guest complexation between cucurbit[8]uril (CB[8]), a methyl viologen (MV) polymer, and mono- and multivalent azobenzene (Azo) functionalized molecules. UV switching of the Azo groups led to fast disruption of the ternary complexes, but to a relatively slow disintegration of the SNPs. Alternating UV and Vis photoisomerization of the Azo groups led to fully reversible SNP disassembly and reassembly. SNPs were only formed with the Azo moieties in the trans and the MV units in the oxidized states, respectively, thus constituting a supramolecular AND logic gate.

The formation of size-tunable, supramolecular nanoparticles (SNPs), employing cucurbit[8]uril-assisted naphthol-viologen charge-transfer complexes, is strongly time and temperature dependent. Yet, the ternary complex formation is fast at all temperatures employed. This indicates that SNP formation requires dynamic disassembly and reassembly of the constituting ternary complex units.

Supramolecular chemistry provides a tool for the formation of highly ordered structures by means of noncovalent interactions. Soft supramolecular nanoparticles are self-assembled nanoassemblies based on small building blocks and stabilized by basic noncovalent interactions, selective host-guest interactions, or a combination of different interaction types. This review provides an overview of the existing approaches for the formation of supramolecular nanoparticles by various types of noncovalent interactions, with a strong focus on host-guest-mediated assemblies. The approaches are ordered based on the nature of the stabilizing supramolecular interaction, while focusing on the aspects that determine the particle structure. Where applicable, the use of these self-assembled nanostructures as vectors in molecular diagnostics and therapeutics is described as well. The stable yet reversible nature of supramolecular interactions and their chemical flexibility offer great prospects for the development of highly engineered nanoparticles which are compatible with the complexity of living systems.

Supramolecular nanoparticles (SNPs) encompass multiple copies of different building blocks brought together by specific noncovalent interactions. The inherently multivalent nature of these systems allows control of their size as well as their assembly and disassembly, thus promising potential as biomedical delivery vehicles. Here, dual responsive SNPs have been based on the ternary host-guest complexation between cucurbit[8]uril (CB[8]), a methyl viologen (MV) polymer, and mono-and multivalent azobenzene (Azo) functionalized molecules. UV switching of the Azo groups led to fast disruption of the ternary complexes, but to a relatively slow disintegration of the SNPs. Alternating UV and Vis photoisomerization of the Azo groups led to fully reversible SNP disassembly and reassembly. SNPs were only formed with the Azo moieties in the trans and the MV units in the oxidized states, respectively, thus constituting a supramolecular AND logic gate.

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.