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 to other cell tracking techniques, is considered a valuable tool to assess effects of cellular therapy. However, in order to allow in vivo tracking of transplanted cells with 10 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 generation of hypointensities to 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 15 within 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", 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 in the synthesis process. Crystalline MnO was not formed 20 when PAA was used as capping agent, since Mn ions (Mn 2+ ) 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 25 the first report to describe the use of an amorphous MnOx as a cell label for MR imaging. 65 may provide a simple, rapid (within minutes), effective, low energy-consuming, environmentally friendly "green" synthesis method for producing inorganic nanostructures with controllable characteristics as well [8,14,18,19].

Design of manganese-based nanomaterials for pharmaceutical and biomedical applications

“…[136][137][138] Synthetic polymers such as poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAA) have been investigating to increase the aqueous dispersibility of MnO NSs. 64 Highly hydrophilic pegylated bis-phosphate dendrons (PDns) have been used as a coating substance for ultrasmall MnO NPs, which improved their colloidal stability, retention and clearance (excretion efficiency) from the body (Fig. 3b).…”

“…No cell death was observed even after treatment with 40 mg mL À1 indicates good cytocompatibility of the MnO NPs. 64 Recently, mixed metal nanocomposites also demonstrated the targeted chemo-phototherapy. The synthesized prepared nanocomposites indicated promising cell viability up to 87%.…”

“…The amorphous MnO nanoparticles exhibited a bright signal enhancement on MR images due to the short relaxation time than those of the crystalline MnO NPs. 64 In an interesting study, it was observed that the MnO NPs show pH-dependent relaxivity. It showed about 35-folds higher This journal is © The Royal Society of Chemistry 2024 relaxivity at lower/acidic pH than the physiological pH.…”

“…The amorphous MnO nanoparticles exhibited a bright signal enhancement on MR images due to the short relaxation time than those of the crystalline MnO NPs. 64…”

<p>Manganese Oxide Nanoparticles As MRI Contrast Agents In Tumor Multimodal Imaging And Therapy</p>

“…Rosenholm and colleagues modified amorphous MnO x with PVP and poly(acrylic acid) (PAA) to bring a negative charge to the surface (−25.7 ± 1.47 mV), while the hydrodynamic properties and biocompatibility were found to be significantly better than crystallization (MnO). Additionally, the relaxation time of the nanoprobe was approximately 10 times lower than that of the crystalline particles 127. Ren and colleagues used MnO x coated superparamagnetic iron oxide nanoparticles as gates to control the CPT release from mesoporous silica and so achieve the TME-responsive T1/T2 dual-mode MRI-guided pancreatic cancer chemotherapy both in vitro and in vivo 128.…”