Novel, fast-processed crystalline and amorphous manganese oxide nanoparticles for stem cell labeling

Abstract

Magnetic resonance (MR) imaging, with its inherent good spatial resolution and without tissue penetration depth limitations associated with other cell tracking techniques, is considered a valuable tool to assess the effects of cellular therapy. However, in order to allow in vivo tracking of transplanted cells with MRI, the cells must be labeled with contrast agents, usually in the form of magnetic or paramagnetic nanoparticles. Typically these are iron oxides, which are associated with a number of drawbacks related e.g. to the generation of hypointensities of the MR image due to signal loss. In this study, two chemically distinct manganese oxide-based nanostructures were developed and their feasibility as labels for human mesenchymal stem cells (hMSCs) was investigated. The ability to monitor the produced particles alone or within the labeled cells in vitro using MR imaging was further evaluated. Two novel synthetic approaches, the polyol process and microwave digestion, were combined to yield a “green”, and extremely rapid means of producing water-dispersible crystalline (MnO) and amorphous (MnOx) manganese oxides. To increase their water dispersability, capping agents in the form of organic polymers, poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAA), were added to the synthesis process. Crystalline MnO was not formed when PAA was used as the capping agent, since Mn ions (Mn²⁺) cannot be hydrolyzed to Mn(OH)₂, which is an intermediate step in the formation of MnO, under the acidic conditions provided by PAA. PVP, on the other hand, served to induce a spherical shape to the formed nanocrystals. Remarkably, the relaxation times of the as-prepared amorphous MnOx were significantly shorter than those of their crystalline counterparts, and the biocompatibility was also higher for MnOx. To the best of our knowledge, this is the first report which describes the use of an amorphous MnOx as a cell label for MR imaging.