Think how unpleasant it is to wrap a gift in a box that is too small. Sometimes you just need a bigger box. Nanostructures are small artificial containers that can be used to deliver therapeutic drugs to specific areas of the body. But some drug molecules are like gifts: too big for standard-size nanocage “boxes”. Now, in a paper published today (April 6) in Nature Synthesis, researchers at the University of Cambridge describe how they built ultra-large nanocages that could be used to deliver even larger cargoes of drugs. simple building blocks.
The rational management of self-assembly cages of this type often presents considerable problems. So instead of following traditional self-assembly methods, the team decided to use a simple building block process inspired by natural biological systems. Using this new method, they were able to create progressively larger artificial nanocages, the largest of which had a volume of more than 92 cubic nanometers, the largest volume of ligand-enclosed lumen ever achieved.
“The study’s findings are significant because they show how we can build ever-larger complex, functional structures out of simple building blocks.”
Dr. Kai Wu, a postdoctoral researcher in the Nitschke lab in the Yusuf Hamied Department of Chemistry,
Simple building blocks
Larger cages have been reported but have more open ligand frameworks, which are not as useful because these cages cannot bind cargo. Potential “guest” molecules slip between the widely spaced rods unless they are covalently attached to the “host” structure.
“The results of this study are important because they show how we can build larger, more complex functional structures using simple building blocks,” said first author Dr. Kai Wu, a postdoctoral fellow in the Nitschke lab in the Yusuf Hamied Department of Chemistry. “
Higher load
Ultra-large nanocages have potential applications in areas such as drug delivery and biotechnology, where they can be used to deliver larger therapeutic biomolecules to specific parts of the body. The researchers also suggest that the large lumen of the nanocage can serve as a platform for binding large biomolecules, such as hydrophobic membrane proteins or proteases, which can be used in drug discovery and development.
“Overall, this research expands our understanding of how to create nanoscale structures and may have practical implications in a variety of fields,” Wu said.
Professor Jonathan Nitschke, who led the research, said: “This work, sponsored in part by Astex Pharmaceuticals under its Sustainable Innovation Postdoc program, aims to have a real impact on the development of new medicines.”
More information: Jonathan Nitschke, Systematic construction of progressively larger capsules from a fivefold linking pyrrole-based subcomponent, Nature Synthesis (2023). DOI: 10.1038/s44160-023-00276-9. www.nature.com/articles/s44160-023-00276-9
