Cyclodextrin-based supramolecular nanoparticles mediated by host-guest and electrostatic interactions: from self-assembly properties to biomedical applications

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Supramolecular nanoparticles (SNPs) have emerged recently as a novel and powerful tool for new developments in nanomedicine. The high versatility of SNPs together with their modular character make them ideal for various biomedical applications. In particular the modular character brings the possibility of easily incorporating targeting moieties, imaging agents, and drug molecules. In recent years, several biomedical systems based on SNPs underwent clinical studies, and some of them have been approved to be used in humans. Most SNPs rely on the assembly of multiple (multivalent) host and guest moieties which have been anchored to building blocks such as molecules, biomolecules, polymers, dendrimers, and inorganic nanoparticles. However, other non-covalent, most notably electrostatic, interactions are usually also involved in their formation. The interplay between the electrostatic and the multivalent host-guest interactions has often been ignored. The work described in this thesis aims to clarify this important aspect of SNP formation, which is essential to understand SNP characteristics such as SNP assembly mechanism, kinetics, disassembly, and stability. In summary, the work described in this thesis provides a new strategy for the formation of SNPs using negatively charged and linear polymers. The importance of the fragile balance between the forces which govern the formation and stability of these SNPs is highlighted. Also, the encapsulation and stimulated release of peptide cargo in these SNPs has been reported. Finally, the importance of the morphology and charge of the guest component on the formation of hybrid clusters was evaluated. These findings are essential for understanding the mechanisms underlying SNP formation, as well as of the encapsulation and release of charged cargo into/from charged SNPs, both of which are of utmost importance for therapeutic applications such as drug and gene delivery. In the area of lanthanide-based NPs, exploring new ways of synthesizing them and studying the characteristics of hybrid organic-inorganic SNPs based on these particles, may lead to a better and more versatile use of this interesting class of nanomaterials, which are becoming more and more important in the bioimaging world. Thus, we hope that the knowledge provided in this thesis will further the development of SNPs as drug carriers and bioimaging agents in nanomedicine.