Original: https://doi.org/10.1002/advs.202413201
Phosphate and phosphonate drugs play important roles in living organisms. They help regulate biological processes and have many medical uses, such as fighting viruses, bacteria, cancers, and inhibiting certain enzymes. However, their full therapeutic potential has not been realized because current nanoengineering methods are limited.
This study introduces a new strategy to create nanodrugs from phosphate and phosphonate compounds. The method takes advantage of the different ways polyphenols and phosphate/phosphonate groups bind to metal ions. Using metal-phenolic networks (MPNs) as templates, researchers can build many kinds of phosphate/phosphonate-based nanodrugs by letting the drugs compete for coordination with the metal ions.
Because the coordination bonds inside these nanostructures are dynamic, the resulting nanodrugs can respond to specific stimuli, allowing for targeted drug release and therapy.
As a demonstration, the researchers used Fe3+ ions and galangin to form an MPN template. They then used zoledronic acid and cGAMP as competitive agents, and loaded the chemotherapy drug DOX to create a nanodrug called DOX@Fe-galangin@Fe-zoledronic acid-cGAMP.
The results show that this nanodrug can trigger pyroptosis, activate the cGAS-STING immune pathway, kill breast tumor cells with high precision, and stimulate an immune response that also fights lung and bone metastases.
Since this competitive coordination strategy can be applied to many different phosphate and phosphonate drugs, it offers strong potential for improving clinical performance and supporting the development of advanced nanodrugs for complex medical treatments.