The team – led by James Crowley at the University of Otago – tested the new method using the cancer medication cisplatin. First they encapsulated the agent in the cage – which comprises an assemblage of simple tripyridyl ligands - before triggering its release by adding Cl- or 4-dimethylaminopyridine (DMAP).
The DMAP competes for binding sites with the cage's PdII centres, thereby breaking down the construction of the cage and releasing the cisplatin held within.
In the study, Crowley wrote: “This is the first crystallographically characterised example of a discrete metallosupramolecular cage encapsulating an FDA-approved inorganic drug molecule.
“This host–guest chemistry could open the way to relatively unexplored methods of drug delivery, which circumvent the malicious side effects and drug resistance associated with cisplatin and other anticancer therapeutics.”
Open and shut
The researchers believe the finding – detailed in Stimuli-responsive Pd2L4 metallosupramolecular cages: towards targeted cisplatin drug delivery – is particularly interesting because it demonstrates a rarely seen ability – specifically that the cage can be reformed after it has been unlocked.
They explained that: “Somewhat surprisingly, despite the considerable interest in synthetic molecular machines, there are very few examples of the reversible stimuli responsive disassembly/reassembly of metallosupramolecular cages reported.
Crowley’s team claim they successfully induced reassembly by introducing Ag+ ions, which remove the DMAP molecules and prompt spontaneous reformation of the cage structure.
“This property is particularly desirable in the context of drug delivery as it would potentially enable the targeted release of an encapsulated drug from the metallosupramolecular cages at the site within the body where it is most needed.”
The team say that future research will be focus on increasing the stability of the cage and host–guest adducts under aqueous or biologically relevant conditions.
Biological studies are currently underway to investigate the technology’s capability to be internalised within cells and to examine their cytotoxic properties.