Self-assembled and responsive supramolecular nanoparticles mediated by cucurbit[8]uril host-guest interactions

Abstract

Supramolecular nanoparticles (SNPs) have gained large interest in nanoscience because stable, but reversible three-dimensional assemblies can be used for a variety of applications, ranging from stimuli-responsive and self-healing materials to biomedical applications. In particular soft SNPs are promising candidates in biomedicine for drug delivery and diagnosis. The versatility of the SNP toolbox concept enables the easy decoration of SNPs with specific cell-targeting molecules and the incorporation of several small molecules, such as drugs or imaging agents, into the SNPs. Thereby, drug and gene delivery vehicles have been developed, some of which are currently being tested in clinical studies as cancer therapeutics. At the same time, many of the underlying self-assembly and colloidal properties of these particles remain unclear, as well as the integration of stimulus-responsive properties for controlled disassembly and release. In summary, the work described in this thesis provides a general strategy for the development of supramolecular nanoparticles mediated by cucurbit[8]uril host-guest interactions while specific attention is paid to the understanding of SNP formation, stabilization, size tunability and triggered disassembly. Based on the heteroternary inclusion of guest molecules into cucurbit[8]uril, the formation of SNPs with highly controllable sizes, diverse shell functionalities and different responses to stimuli have been reported. The time and temperature dependent SNP self-assembly as well as the different disassembly pathways give new insight in the formation and disintegration of SNPs and their dynamics. This is essential for the development of effective carriers that can potentially be used in biomedical applications and meet the stringent and multifaceted demands of living systems. We expect that, upon inclusion of active compounds, these SNPs can provide a new generation of functional, biomedically relevant nanodevices.