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Design of Superparamagnetic Nanoparticles for Magnetic Particle Imaging (MPI)  [PDF]
Yimeng Du,Pui To Lai,Cheung Hoi Leung,Philip W. T. Pong
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms140918682
Abstract: Magnetic particle imaging (MPI) is a promising medical imaging technique producing quantitative images of the distribution of tracer materials (superparamagnetic nanoparticles) without interference from the anatomical background of the imaging objects (either phantoms or lab animals). Theoretically, the MPI platform can image with relatively high temporal and spatial resolution and sensitivity. In practice, the quality of the MPI images hinges on both the applied magnetic field and the properties of the tracer nanoparticles. Langevin theory can model the performance of superparamagnetic nanoparticles and predict the crucial influence of nanoparticle core size on the MPI signal. In addition, the core size distribution, anisotropy of the magnetic core and surface modification of the superparamagnetic nanoparticles also determine the spatial resolution and sensitivity of the MPI images. As a result, through rational design of superparamagnetic nanoparticles, the performance of MPI could be effectively optimized. In this review, the performance of superparamagnetic nanoparticles in MPI is investigated. Rational synthesis and modification of superparamagnetic nanoparticles are discussed and summarized. The potential medical application areas for MPI, including cardiovascular system, oncology, stem cell tracking and immune related imaging are also analyzed and forecasted.
Citrate capped superparamagnetic iron oxide nanoparticles used for hyperthermia therapy  [PDF]
Elham Cheraghipour, Sirus Javadpour, Ali Reza Mehdizadeh
Journal of Biomedical Science and Engineering (JBiSE) , 2012, DOI: 10.4236/jbise.2012.512089
Abstract: Superparamagnetic magnetite nanoparticles (MNP) of about 10 nm were designed with proper physico-chemical characteristics by an economic, biocompatible chemical coprecipitation of Fe2+ and Fe3+ in an ammonia solution, for hyperthermia applications. Synthetic methodology has been developed to get a well dispersed and homogeneous aqueous suspension of MNPs. Citric acid was used to stabilize the magnetite particle suspension, it was anchored on the surface of freshly prepared MNPs by direct addition method. Carboxylic acid terminal group not only render the particles more water dispersible but also provides a site for further surface modification. The naked MNPs are often insufficient for their stability, hydrophilicity and further functionalization. To overcome these limitations, citric acid was conjugated on the surface of the MNPs. The microstructure and morphology of the nanoparticles were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM), and the interaction between citric acid and MNPs were characterized by Fourier transform infrared spectroscopy (FTIR), whereas the magnetic properties were investigated by vibrating sample magnetometry (VSM). Magnetic measurement revealed that the saturation magnetization of the nanoparticles was 74 emu/g and the nanoparticles were superparamagnetic at room temperature. We also have analyzed the potential of these particles for hyperthermia by determination of the specific absorption rate, the temperature increase (ΔT) of the particles was 37oC. These ferrofluids with high self-heating capacity are a promising candidate for cancer hyperthermia treatment.
Live Tissue Imaging Shows Reef Corals Elevate pH under Their Calcifying Tissue Relative to Seawater  [PDF]
Alexander Venn, Eric Tambutté, Michael Holcomb, Denis Allemand, Sylvie Tambutté
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020013
Abstract: The threat posed to coral reefs by changes in seawater pH and carbonate chemistry (ocean acidification) raises the need for a better mechanistic understanding of physiological processes linked to coral calcification. Current models of coral calcification argue that corals elevate extracellular pH under their calcifying tissue relative to seawater to promote skeleton formation, but pH measurements taken from the calcifying tissue of living, intact corals have not been achieved to date. We performed live tissue imaging of the reef coral Stylophora pistillata to determine extracellular pH under the calcifying tissue and intracellular pH in calicoblastic cells. We worked with actively calcifying corals under flowing seawater and show that extracellular pH (pHe) under the calicoblastic epithelium is elevated by ~0.5 and ~0.2 pH units relative to the surrounding seawater in light and dark conditions respectively. By contrast, the intracellular pH (pHi) of the calicoblastic epithelium remains stable in the light and dark. Estimates of aragonite saturation states derived from our data indicate the elevation in subcalicoblastic pHe favour calcification and may thus be a critical step in the calcification process. However, the observed close association of the calicoblastic epithelium with the underlying crystals suggests that the calicoblastic cells influence the growth of the coral skeleton by other processes in addition to pHe modification. The procedure used in the current study provides a novel, tangible approach for future investigations into these processes and the impact of environmental change on the cellular mechanisms underpinning coral calcification.
Comparison of Two Ultrasmall Superparamagnetic Iron Oxides on Cytotoxicity and MR Imaging of Tumors
Mulan Li, Hoe Suk Kim, Lianji Tian, Mi Kyung Yu, Sangyong Jon, Woo Kyung Moon
Theranostics , 2012,
Abstract: Purpose: This study was performed to compare the cytotoxicity and magnetic resonance (MR) contrast in diverse cultured cells and xenograft tumors models of two ultra-small superparamagnetic iron oxides (USPIOs), thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and monocrystalline iron oxide nanoparticles (MION-47). Materials and methods: Transmission electron microscopy (TEM) images and R2 relaxivity values of the TCL-SPION and MION-47 were obtained and the cell viability and cell growth velocity of treated and untreated human fibroblasts and human umbilical vein endothelial cells (HUVEC) were evaluated. The effect of TCL-SPION and MION-47 on the secretion of interlukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), the production of nitric oxides and the mitochondrial membrane potentials in murine macrophage cells (RAW264.7) was compared. Human hepatocellular carcinoma cells (HepG2, 5x105) were subcutaneously injected into nude mice (BALB/c) and in vivo MR imaging of tumors before and after injection with TCL-SPION or MION-47 (12.5 mg Fe/kg) was performed on a 1.5 Tesla MRI scanner. Results: On TEM images, the average core diameter of TCL-SPION was 9 nm whereas that of MION-47 was 5 nm. TCL- SPION (345.0 ± 6.2 mM-1sec-1) had higher relaxivity (R2) than MION-47 (130.7 ± 1.1 mM-1sec-1). Significant changes in cell viability and growth were not found in human fibroblasts and HUVEC exposed to TCL-SPION and MION-47. However, IL-6 and TNF-α secretions increased dose-dependently and significantly in the macrophages treated with MION-47 or TCL-SPION. TCL-SPION had a lower stimulatory effect on IL-6 secretions than did MION-47 (P <0.05) and nitric oxides were produced in the macrophages by MION-47 but not TCL-SPION. A change in the mitochondrial membrane potential of the macrophages was observed 24 hours after the exposure, and MION-47 induced more collapses of the mitochondrial membrane potential than did TCL-SPION. In the in vivo MR imaging, 33.0 ± 1.3% and 7.5 ± 0.4% signal intensity decrease on T2*-weighted images was observed in the tumors injected with TCL-SPION and MION-47, respectively. Conclusion: Due to the modified surface properties and larger core size of its iron oxide nanoparticles, TCL-SPION achieves lower cytotoxicity and better tumor MR contrast than MION-47. Our study suggests that TCL-SPION may be used as a new platform for tumor imaging and therapy monitoring.
Bifunctional Silica-Coated Superparamagnetic FePt Nanoparticles for Fluorescence/MR Dual Imaging
Syu-Ming Lai,Tsiao-Yu Tsai,Chia-Yen Hsu,Jai-Lin Tsai,Ming-Yuan Liao,Ping-Shan Lai
Journal of Nanomaterials , 2012, DOI: 10.1155/2012/631584
Abstract: Recently, superparamagnetic chemically disordered face-centered cubic (fcc) FePt nanoparticles have been demonstrated as superior negative contrast agents for magnetic resonance imaging (MRI). However, their low intracellular labeling efficiency has limited the potential usage and the nanotoxicity of the particles requires attention. We have developed fluorescein isothiocyanate-incorporated silica-coated FePt (FePt@SiO2-FITC) nanoparticles that exhibited not only a significant T1 and T2 MR contrast abilities but also a fluorescent property without significant cytotoxicities. These results suggest that silica-coated superparamagnetic FePt nanoparticles are potential nanodevices for the combination of fluorescence and MRI contrast used for cancer diagnosis.
Relaxometry and dephasing imaging of superparamagnetic magnetite nanoparticles using a single qubit  [PDF]
Dominik Schmid-Lorch,Thomas H?berle,Friedemann Reinhard,Andrea Zappe,Michael Slota,Lapo Bogani,Amit Finkler,J?rg Wrachtrup
Physics , 2015, DOI: 10.1021/acs.nanolett.5b00679
Abstract: To study the magnetic dynamics of superparamagnetic nanoparticles we use scanning probe relaxometry and dephasing of the nitrogen-vacancy (NV) center in diamond, characterizing the spin-noise of a single 10-nm magnetite particle. Additionally, we show the anisotropy of the NV sensitivity's dependence on the applied decoherence measurement method. By comparing the change in relaxation (T 1 ) and dephasing (T 2 ) time in the NV center when scanning a nanoparticle over it, we are able to extract the nanoparticle's diameter and distance from the NV center using an Ornstein-Uhlenbeck model for the nanoparticle's fluctuations. This scanning-probe technique can be used in the future to characterize different spin label substitutes for both medical applications and basic magnetic nanoparticle behavior.
Use of Superparamagnetic Nanoparticle/Block Copolymer Electrostatic Complexes as Contrast Agents in Magnetic Resonance Imaging  [PDF]
Jean-Francois Berret,Regis Cartier
Physics , 2007,
Abstract: During the past years we have investigated the complexation between nanocolloids and oppositely charged polymers. The nanocolloids examined were ionic surfactant micelles and inorganic oxide nanoparticles. For the polymers, we used homopolyelectrolytes and block copolymers with linear and comb architectures. In general, the attractive interactions between oppositely charged species are strong and as such, the simple mixing of solutions containing dispersed constituents yield to a precipitation, or to a phase separation. We have developed means to control the electrostatically-driven attractions and to preserve the stability of the mixed solution. With these approaches, we designed novel core-shell nanostructures, e.g. as those obtained with polymers and iron oxide superparamagnetic nanoparticles. In this presentation, we show that electrostatic complexation can be used to tailor new functionalized nanoparticles and we provide examples related to biomedical applications in the domain of contrast agents for Magnetic Resonance Imaging.
Superparamagnetic Iron Oxide Enhanced Magnetic Resonance Imaging in the Detection of Malignant Liver Lesions
Bekir ?a?l?,Osman Temiz?z,Hakan Gen?hella?,Hasan ümit
Balkan Medical Journal , 2011,
Abstract: Objective: To determine the value of superparamagnetic iron oxide (SPIO)-enhanced MR imaging in malignant liver lesions.Materials and Methods: Twenty patients with various hepatic masses or metastases were investigated with 1 tesla MR. T1-weighted FLASH and double- echo TSE T2-weighted sequences were applied before and after contrast injection. “Defining statistics” were prepared according to pre and postcontrast signal intensity measurements. Results: In this study there were 11 patients with metastases, 4 patients with hemangioma, 4 patients with HCC and one patient with a hemangioma and a metastasis at the same time. In cases wheret we found only hemangiomas, in all sequences, S/N ratios (p=0.043) and T2-weighted double-echo TSE with long TE SI change (p=0.043) were significant. While in the hemangiomas in T2-weighted double-echo TSE with long TE there is an decrease in the C/N ratios; in cases with metastasis and HCC, compared to other sequences significant increase in C/N ratio in T2-weighted double-echo TSE with short TE sequences was detected.Conclusion: SPIO-enhanced MR imaging can be used as a non-invasive radiologic technique for the detection focal liver lesions, to determine the number of lesions and also has a value in differentiating the benign lesions (especially hemangiomas) from primary tumors or metastatic malignant lesions.
Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes
Frascione D, Diwoky C, Almer G, Opriessnig P, Vonach C, Gradauer K, Leitinger G, Mangge H, Stollberger R, Prassl R
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S30617
Abstract: rasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes Original Research (3063) Total Article Views Authors: Frascione D, Diwoky C, Almer G, Opriessnig P, Vonach C, Gradauer K, Leitinger G, Mangge H, Stollberger R, Prassl R Published Date May 2012 Volume 2012:7 Pages 2349 - 2359 DOI: http://dx.doi.org/10.2147/IJN.S30617 Received: 06 February 2012 Accepted: 03 March 2012 Published: 09 May 2012 Daniela Frascione,1 Clemens Diwoky,2 Gunter Almer,1,3 Peter Opriessnig,2 Caroline Vonach,1 Kerstin Gradauer,1 Gerd Leitinger,4 Harald Mangge,3 Rudolf Stollberger,2 Ruth Prassl1,5 1Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria; 2Institute of Medical Engineering, University of Technology, Graz, Austria; 3Clinical Institute for Medical and Chemical Laboratory Diagnosis (CIMCL), Medical University, Graz, Austria; 4Institute of Cell Biology, Histology and Embryology, Medical University, Graz, Austria; 5Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria Background: Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magnetic and/or paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). MLs have an advantage over free magnetic nanocores, in that various functional groups can be attached to the surface of liposomes for ligand-specific targeting. We have synthesized PEG-coated sterically-stabilized magnetic liposomes (sMLs) containing ultrasmall superparamagnetic iron oxides (USPIOs) with the aim of generating stable liposomal carriers equipped with a high payload of USPIOs for enhanced MRI contrast. Methods: Regarding iron oxide nanoparticles, we have applied two different commercially available surface-coated USPIOs; sMLs synthesized and loaded with USPIOs were compared in terms of magnetization and colloidal stability. The average diameter size, morphology, phospholipid membrane fluidity, and the iron content of the sMLs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence polarization, and absorption spectroscopy, respectively. A colorimetric assay using potassium thiocyanate (KSCN) was performed to evaluate the encapsulation efficiency (EE%) to express the amount of iron enclosed into a liposome. Subsequently, MRI measurements were carried out in vitro in agarose gel phantoms to evaluate the signal enhancement on T1- and T2-weighted sequences of sMLs. To monitor the biodistribution and the clearance of the particles over time in vivo, sMLs were injected in wild type mice. Results: DLS revealed a mean particle diameter of sMLs in the range between 100 and 200 nm, as confirmed by TEM. An effective iron oxide loading was achieved just for one type of USPIO, with an EE% between 74% and 92%, depending on the initial Fe concentration (being higher for lower amounts of Fe). MRI measurements demonstrated the applicability of these nanostructures as MR
In vivo magnetic resonance imaging tracking of C6 glioma cells labeled with superparamagnetic iron oxide nanoparticles
Mamani, Javier Bustamante;Malheiros, Jackeline Moraes;Cardoso, Ellison Fernando;Tannús, Alberto;Silveira, Paulo Henrique;Gamarra, Lionel Fernel;
Einstein (S?o Paulo) , 2012, DOI: 10.1590/S1679-45082012000200009
Abstract: objective: the aim of the current study was to monitor the migration of superparamagnetic iron oxide nanoparticle (spion)-labeled c6 cells, which were used to induce glioblastoma tumor growth in an animal model, over time using magnetic resonance imaging (mri), with the goal of aiding in tumor prognosis and therapy. methods: two groups of male wistar rats were used for the tumor induction model. in the first group (n=3), the tumors were induced via the injection of spion-labeled c6 cells. in the second group (n=3), the tumors were induced via the injection of unlabeled c6 cells. prussian blue staining was performed to analyze the spion distribution within the c6 cells in vitro. tumor-inducing c6 cells were injected into the right frontal cortex, and subsequent tumor monitoring and spion detection were performed using t2- and t2*-weighted mri at a 2t field strength. in addition, cancerous tissue was histologically analyzed after performing the mri studies. results: the in vitro qualitative evaluation demonstrated adequate distribution and satisfactory cell labeling of the spions. at 14 or 21 days after c6 injection, a spion-induced t2- and t2*-weighted mri signal reduction was observed within the lesion located in the left frontal lobe on parasagittal topography. moreover, histological staining of the tumor tissue with prussian blue revealed a broad distribution of spions within the c6 cells. conclusion: mri analyses exhibit potential for monitoring the tumor growth of c6 cells efficiently labeled with spions.
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