Internalization Of Superparamagnetic Iron Oxide Nanoparticles Research Articles

SPIONs magnetic nanoparticles for MRI applications: Microwave synthesis and physicochemical, magnetic and biological characterizations

More and more biomedical applications used nanoparticles to improve their quality and their possibilities. Among the nanoparticles used, Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are often used because these nanoparticles are biocompatible, non-toxic and the ease of synthesizing them. The aim of this study is to obtain highly water-soluble iron oxide nanoparticles using a microwave process. The SPIONs developped with this technique have a diameter between 2 nm and 4 nm range, are monodisperse and stable in an aqueous media. Indeed, with the microwaves, the control of the temperature is more precise and allows so to obtain nanoparticles with a same diameter. After the synthesis, several characterizations are carried out to determine the shape, the size, the chemical composition, the stability and the magnetic properties. Then, these SPIONs can use to control the regeneration of tissues such as cartilage tissue. For that, SPIONs are internlasized in mesenchymal stromal cells (MSCs) because these cells can to differenciate into all humans cells and allows so to regenerate all tissues: these cells are good candidate for tissue engineering. In this work, the internalization of SPIONs and the cytotocixity are studied and confirm the biocompatibility of our SPIONs. Then, for the control of the regeneration of tissues, relaxometry and MRI (Magnetic Resonance Imaging) of SPIONs are realized to compare with the commercial contrast agent present (Endorem®). For our SPIONs, the values of transverse and longitudinal relaxivities are high and in the same order to Endorem®.

MRI tracking of human Wharton's jelly stem cells seeded onto acellular dermal matrix labeled with superparamagnetic iron oxide nanoparticles in burn wounds.

In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies. This study investigated tracking of human Wharton's jelly stem cells (hWJSCs) seeded onto an acellular dermal matrix (ADM) and labeled with superparamagnetic iron oxide nanoparticles (SPIONs) by magnetic resonance imaging (MRI) in burn injury. The hWJSCs were characterized and assessed for growth kinetics. A total of 30 rats were enrolled in three equal groups. Group 1 underwent scald burn injury left without treatment, the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM. Tensile strength was evaluated before and after interventions, real time PCR assessed apoptosis, and Prussian blue staining, scanning electron microscopy (SEM) and MRI were used for the tracking of labeled cells. The hWJSCs exhibited mesenchymal stem cell properties. Population doubling time was 40.1 hours. SPIONs did not show any toxic effect. The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression. Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining, SEM and MRI until day 21. There was a significant difference between the Young's moduli of normal skin and the group receiving hWJSCs seeded onto an ADM. Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo. This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

MRI-Tracking of Dental Pulp Stem Cells In Vitro and In Vivo Using Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles.

The aim of this study was to track dental pulp stem cells (DPSCs) labeled with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) using magnetic resonance imaging (MRI). Dental pulp was isolated from male Sprague Dawley rats and cultured in Dulbecco’s modified Eagle’s medium F12 (DMEM-F12) and 10% fetal bovine serum. Effects of SPIONs on morphology, viability, apoptosis, stemness, and osteogenic and adipogenic differentiation of DPSCs were assessed. Prussian blue staining and MRI were conducted to determine in vitro efficiency of SPIONs uptake by the cells. Both non-labeled and labeled DPSCs were adherent to culture plates and showed spindle-shape morphologies, respectively. They were positive for osteogenic and adipogenic induction and expression of cluster of differentiation (CD) 73 and CD90 biomarkers, but negative for expression of CD34 and CD45 biomarkers. The SPIONs were non-toxic and did not induce apoptosis in doses less than 25 mg/mL. Internalization of the SPIONs within the DPSCs was confirmed by Prussian blue staining and MRI. Our findings revealed that the MRI-based method could successfully monitor DPSCs labeled with dextran-coated SPIONs without any significant effect on osteogenic and adipogenic differentiation, viability, and stemness of DPSCs. We provided the in vitro evidence supporting the feasibility of an MRI-based method to monitor DPSCs labeled with SPIONs without any significant reduction in viability, proliferation, and differentiation properties of labeled cells, showing that internalization of SPIONs within DPSCs were not toxic at doses less than 25 mg/mL. In general, the SPION labeling does not seem to impair cell survival or differentiation. SPIONs are biocompatible, easily available, and cost effective, opening a new avenue in stem cell labeling in regenerative medicine.

Toxicity of superparamagnetic iron oxide nanoparticles to the microalga Chlamydomonas reinhardtii

Superparamagnetic iron oxide nanoparticles (SPION) have been widely studied for different biomedical and environmental applications. In this study we evaluated the toxicity and potential alterations of relevant physiological parameters caused to the microalga Chlamydomonas reinhardtii (C. reinhardtii) upon exposure to SPION. The results showed dose-dependent toxicity. A mechanistic study combining flow cytometry and physiological endpoints showed a toxic response consisting of a decrease in metabolic activity, increased oxidative stress and alterations in the mitochondrial membrane potential. Additionally, and due to the light absorption of SPION suspensions, we observed a significant shading effect, causing a marked decrease in photosynthetic activity. In this work, we demonstrated for the first time, the internalization of SPION by endocytosis in C. reinhardtii. These results demonstrated that SPION pose a potential risk for the environment if not managed properly.

Susceptibility-weighted imaging for stem cell visualization in a rat photothrombotic cerebral infarction model

In cell therapy, magnetic resonance imaging (MRI) has been used to visualize superparamagnetic iron oxide (SPIO)-labeled stem cells homing to a lesion. Improving traceability is to utilize the sequence that maximizes sensitivity to the susceptibility effect of SPIO. To explore the best method by comparing the MRI sequences to visualize mesenchymal stem cells (MSCs) labeled with SPIO. Human bone marrow (hBM)-derived MSCs were labeled by internalization of SPIO nanoparticles. In vitro MRI was performed for the SPIO-labeled hBM-MSCs in tubes with T2-weighted (T2W), T2*-weighted (T2*W), and susceptibility-weighted images (SWI). Contrast-to-noise ratio (CNR) and volumes of dark signal of SPIO-labeled hBM-MSCs were obtained on images of each sequence. Photothrombotic cerebral infarction (PTCI) was induced in eight rats, and 2.5 × 10(5) SPIO-labeled hBM-MSCs were infused through the tail vein on the third day. In vivo MRI of the rat brain was performed using a 3.0 T MRI on the first, third, seventh, and 14th days. CNRspio was obtained on T2W imaging, T2*W imaging, and SWI. The dark signals were compared with the SPIO-positive cells of Prussian blue staining. In vitro MRI of 5 × 10(5) SPIO-labeled hBM-MSCs showed the CNR and volume of dark signal to be 63, 517 mm(3) in SWI, 41, 228 mm(3) in T2*W imaging, and 56, 41 mm(3) in T2W imaging, respectively. In vivo MRI showed a dark signal surrounding the high signal intensity of PTCI. Pathologically, the dark signals were matched with SPIO-labeled hBM-MSC in the corresponding rat. The dark signal was most prominent in SWI, then T2*W imaging, and finally in T2W imaging (P <0.05). In SWI, other causes of dark signals were matched with the veins and the choroid plexuses on histopathology. SWI can visualize SPIO-labeled hBM-MSCs more sensitively, earlier, and with larger size and greater contrast than T2W imaging and T2*W imaging.