Cyclodextrins are large, cone-shaped sugar ring molecules with inner cavities that exhibit an exceptional propensity for the binding of hydrophobic compounds to form complexes. The inner cavity also allows multiple cyclodextrin molecules to be threaded onto linear polymers through intermolecular interactions, generating necklace-like molecules called polyrotaxanes.

Cyclodextrins act as insulating sheaths for conducting polymers, thus enhancing electrical transport and chemical stability. Cyclodextrin polyrotaxanes have also shown promise in facilitating the delivery of protein and peptide drugs, as well as DNA into cells.

Fig. 1: Schematic diagrams of nanocapsules composed of polyrotaxanes with (a) four or (b) six cyclodextrins threaded onto each polyethylene glycol chain. The number of cyclodextrins determines the thickness of the shell.

Now, Jun Li and Yun-Long Wu of the National University of Singapore and A*STAR1 have created new polymer nanocapsules by anchoring cyclodextrin polyrotaxanes onto gold nanoparticles (Fig. 1).

Polymer nanocapsules, which can be prepared by various polymerization techniques, are hollow, nanometer-sized spheres that may serve as vessels for the storage and transport of biologically relevant entities. In their innovative approach, Li and Wu built polyrotaxanes using polyethylene glycol — a biocompatible linear polymer. They first anchored the polymer strands onto the gold nanoparticles before threading the cyclodextrins. They then capped the polymer extremities with bulky stoppers to prevent the cyclodextrins from slipping off the chains. To consolidate a hydrophilic shell around the nanoparticles, the polyrotaxanes were cross-linked with a highly branched polymer, and the nanoparticle cores were finally dissolved using a sodium cyanide solution, yielding polymer nanocapsules.

The unique spectroscopic properties of the gold nanoparticle template allowed the researchers to monitor each step in the nanocapsule synthesis. They revealed that, instead of agglomerates, the gold nanoparticles formed well-dispersed, well-defined islands coated with the polyrotaxanes.

Unlike previous methods based on conventional cyclodextrin polymers, the anchored polyrotaxanes resulted in nanometer-thick shells with superior robustness. “The shell thickness can be tuned with the length of the polyrotaxane columns, which can be easily controlled by the molecular weight of polymer that is grafted on the gold nanoparticles,” says Li. “Nanocapsules with ligands attached to the shells are being developed in our lab. Drugs and nucleic acids will be encapsulated into the nanocapsules for targeted drug and gene delivery.”

The researchers also plan to remove the polyethylene glycol threads to generate porous nanocapsules and exploit the cyclodextrin cavities.