Alginate-coated magnetic nanoparticles for noninvasive MRI of extracellular calcium

Nanoparticles (NPs) have great potential to increase the diagnostic capacity of many imaging modalities. MRI is currently regarded as the method of choice for the imaging of deep tissues, and metal ions, such as calcium ions (Ca²⁺), are essential ingredients for life. Despite the tremendous importance of Ca²⁺ for the well-being of living systems, the noninvasive determination of the changes in Ca²⁺ levels in general, and extracellular Ca²⁺ levels in particular, in deep tissues remains a challenge. Here, we describe the preparation and contrast mechanism of a flexible easy to prepare and selective superparamagnetic iron oxide (SPIO) NPs for the noninvasive determination of changes in extracellular Ca²⁺ levels using conventional MRI. We show that SPIO NPs coated with monodisperse and purified alginate, having a specific molecular weight, provide a tool to selectively determine Ca²⁺ concentrations in the range of 250μm to 2.5mm, even in the presence of competitive ions. The alginate-coated magnetic NPs (MNPs) aggregate in the presence of Ca²⁺, which, in turn, affects the T₂ relaxation of the water protons in their vicinity. The new alginate-coated SPIO NP formulations, which have no effect on cell viability for 24h, allow the detection of Ca²⁺ levels secreted from ischemic cell cultures and the qualitative examination of the change in extracellular Ca²⁺ levels in vivo. These results demonstrate that alginate-coated MNPs can be used, at least qualitatively, as a platform for the noninvasive MRI determination of extracellular Ca²⁺ levels in myriad in vitro and in vivo biomedical applications.