Siderophores for medical applications: Imaging, sensors, and therapeutics

Siderophores are low-molecular-weight chelators produced by microorganisms to scavenge iron from the environment and deliver it to cells via specific receptors. Tremendous researches on the molecular basis of siderophore regulation, synthesis, secretion, and uptake have inspired their diverse applications in the medical field. Replacing iron with radionuclides in siderophores, such as the most prominent Ga-68 for positron emission tomography (PET), carves out ways for targeted imaging of infectious diseases and cancers. Additionally, the high affinity of siderophores for metal ions or microorganisms makes them a potent detecting moiety in sensors that can be used for diagnosis. As for therapeutics, the notable Trojan horse-inspired siderophore-antibiotic conjugates demonstrate enhanced toxicity against multi-drug resistant (MDR) pathogens. Besides, siderophores can tackle iron overload diseases and, when combined with moieties such as hydrogels and nanoparticles, a wide spectrum of iron-induced diseases and even cancers. In this review, we briefly outline the related mechanisms, before summarizing the siderophore-based applications in imaging, sensors, and therapeutics.