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

Yeast-derived β-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 T₁ 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 T₁ 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 T₁ relaxation of the water protons.