Binding and Release of FeIII Complexes from Glucan Particles for the Delivery of T1 MRI Contrast Agents

Yeast-derived beta-glucan particles (GPs) are a class of microcarriers under development for the delivery of drugs and imaging agents to immune-system cells for theranostic approaches. However, the encapsulation of hydrophilic imaging agents in the porous GPs is challenging. Here, we show that the unique coordination chemistry of Fe-III-based macrocyclic T-1 MRI contrast agents permits facile encapsulation in GPs. Remarkably, GPs labeled with the simple Fe-III complexes are stable under physiologically relevant conditions, despite the absence of amphiphilic groups. In contrast to the free Fe-III coordination complex, the labeled Fe-III-GPs have lowered T-1 relaxivity and act as a silenced form of the contrast agent. Addition of a fluorescent tag to the Fe-III complex produces a bimodal agent to further enable tracking of the nanoparticles and to monitor release. Treatment of the iron-labeled GPs with a maltol chelator or with mildly acidic conditions releases the intact iron complex and restores enhanced T-1 relaxation of the water protons.