Browsing by Subject "Superparamagnetic iron oxide nanoparticles"

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Open Access
Amphiphilic peptide coated superparamagnetic iron oxide nanoparticles for in vivo MR tumor imaging
(Royal Society of Chemistry, 2016) Ozdemir, A.; Ekiz, M. S.; Dilli, A.; Güler, Mustafa O.; Tekinay, A. B.
Magnetic resonance imaging (MRI) is a noninvasive imaging technique that provides high spatial resolution and depth with pronounced soft-tissue contrast for in vivo imaging. A broad variety of strategies have been employed to enhance the diagnostic value of MRI and detect tissue abnormalities at an earlier stage. Superparamagnetic iron oxide nanoparticles (SPIONs) are considered to be suitable candidates for effective imaging due to their small size, versatile functionality and better biocompatibility. Here, we demonstrate that coating SPIONs with proline-rich amphiphilic peptide molecules through noncovalent interactions leads to a water-dispersed hybrid system suitable as an MRI contrast agent. Cellular viability and uptake of amphiphilic peptide coated SPIONs (SPION/K-PA) were evaluated with human vascular endothelial cells (HUVEC) and estrogen receptor (ER) positive human breast adenocarcinoma (MCF-7) cells. The efficiency of SPION/K-PA as MRI contrast agents was analyzed in Sprague-Dawley rats with mammary gland tumors. MR imaging showed that SPION/K-PA effectively accumulated in tumor tissues, enhancing their imaging potential. Although nanoparticles were observed in reticuloendothelial system organs (RES) and especially in the liver and kidney immediately after administration, the MR signal intensity in these organs diminished after 1 h and nanoparticles were subsequently cleared from these organs within two weeks. Histological observations also validated the accumulation of nanoparticles in tumor tissue at 4 h and their bioelimination from the organs of both healthy and tumor-bearing rats after two weeks.
Open Access
Biomacromolecules, molecules and functional nanoparticles for therapeutic and diagnostic applications
(2016-03) Özdemir, Ayşe
Cancer is one of the most important global health problem. In the last decade, researchers have focused on the development of novel sensitive diagnostic agents and potential therapeutic molecules to further contribute to the success of cancer treatment and increase survival rates of cancer patients. Magnetic resonance imaging (MRI) is a powerful diagnostic tool and used in clinics for cancer imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as a negative contrast agent to increase sensitivity of MRI. SPIONs can be coated with biocompatible natural or synthetic materials to maintain stability and improve their blood distribution profile. SPIONs can also be non-covalently functionalized with peptide amphiphile (PA) molecules through hydrophobic interactions to render them water soluble and biocompatible. In addition, several efforts have been made to improve specificity and sensitivity of SPIONs by attaching cancer targeting agents such as peptides. For cancer therapy, metal based drugs have attracted attention because of their biological and pharmaceutical properties over the past decades. The understanding of interactions between potential agents and biomolecules is important for designing novel anticancer drugs against tumors to overcome the toxicity of currently used chemotherapeutic drugs and achieve more precision. Herein, I investigated the potential of proline-rich PA coated SPIONs as a negative contrast agent for cancer diagnosis by MRI. To achieve water solubility and cancer targeting, positively charged K and LPPR peptide sequences were presented on the PA micelles. PA functionalization provided a water-dispersible hybrid system. Biocompatibility and efficient uptake of the SPIONs were found to be improved with PA coating. This hybrid system provided enhancement in the MR imaging of tumor tissue in chemically induced breast cancer model. In addition, in vivo experiments and histological examinations revealed the biodistribution and bioelimination profile of the nanoparticles. These SPION/PA system can potentially be used as a contrast agent in cancer diagnosis by MRI. In addition, I analyzed the interactions between metal based molecules that can be used as cancer therapeutics and calf thymus DNA or human serum albumin (HSA) by spectroscopic and calorimetric methods which showed the binding modes, affinities and the effects on the structure of these biomacromolecules. Although similar structures demonstrated similar binding characteristics, each molecule has different association with DNA or HSA. The obtained results are promising for the development of metal or half metal based anticancer agents targeting DNA and carried by HSA.
Open Access
Biomedical applications of peptide nanostructures
(2016-04) Şardan Ekiz, Melis
Thesis (Ph. D.): Bilkent University, Materials Science and Nanotechnology Program, İhsan Doğramacı Bilkent University, 2016.
Open Access
Cancer imaging and treatment monitoring with color magnetic particle imaging
(2021-09) Ütkür, Mustafa
Magnetic particle imaging (MPI) is emerging as a highly promising non-invasive tomographic imaging modality for cancer research. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging tracers in MPI. By exploiting the relaxation behavior of SPIONs, the capabilities of MPI can also be broadened to functional imaging applications that can distinguish different nanoparticles and/or environments. One of the important applications of functional MPI is viscosity mapping, since certain cancer types are shown to have increased cellular viscosity levels. MPI can potentially detect these cancerous tissues through estimating the viscosity levels of the tissue environment. Another important application area of MPI is temperature mapping, since SPIONs are also utilized in magnetic fluid hyperthermia (MFH) treatments and MPI enables localized application of MFH. To achieve accurate temperature estimations, however, one must also take into account the confounding effects of viscosity and temperature on the MPI signal. This dissertation studies relaxation-based viscosity and temperature mapping with MPI, covering the biologically relevant viscosity range (<5 mPa·s) and the therapeutically applicable temperature range (25-45!C). The characterization of the SPION relaxation response was performed on an in-house arbitrarywaveform magnetic particle spectrometer (MPS) setup, and the imaging experiments were performed on an in-house MPI scanner. Both the MPS setup and the MPI scanner were designed and developed as parts of this thesis. The effects of viscosity and temperature on relaxation time constant estimations were investigated, and the sensitivities of MPI to these functional parameters were determined at a wide range of operating points. The relaxation time constants, t’s, were estimated with a technique called TAURUS (TAU, t, estimation via Recovery of Underlying mirror Symmetry), which is based on a linear relaxation equation. Although the nonlinear relaxation behaviors of the SPIONs are highly dependent on the excitation field parameters, SPION type, and the hardware configuration, the results suggest that one-to-one relation between the estimated t and the targeted functional parameters (i.e., viscosity or temperature) can be obtained. According to these results, MPI can successfully map viscosity and temperature, with higher than 30%/mPa/s sensitivity for viscosity mapping and approximately 10%/!C sensitivity for temperature mapping, at 10 kHz drive field frequency. In addition, the results suggest that the simultaneous mapping of viscosity and temperature can be achieved by performing multiple measurements at different drive field frequencies and/or amplitudes. Overall, these findings show that hybrid MPI-MFH systems offer a promising approach for real-time monitored and localized thermal ablation treatment of cancer. The viscosity and temperature mapping capabilities of MPI via relaxation time constant estimation can provide feedback for high accuracy thermal dose adjustment to the cancerous tissues, thereby, increasing the efficacy of the treatment.
Open Access
Manyetik parçacık görüntüleme için sinyal-gürültü oranını eniyileyen görüntü geriçatım tekniği
(Gazi Universitesi Muhendislik-Mimarlik, 2017) Bozkurt, Ecem; Sarıtaş, Emine Ülkü
Magnetic particle imaging (MPI) is a new biomedical imaging modality that images the spatial distribution of superpamagnetic iron oxide nanoparticles. In MPI, the amplitude of the excitation magnetic field that causes the time-varying magnetization response of the nanoparticles is restricted by the nerve stimulation safety limits. Hence, the region to be imaged is divided into small sections and scanned as overlapping partial fields-of-view. The nanoparticle signal at the excitation frequency is lost during the filtering process of the direct feedthrough signal induced on the receive coil due to the excitation field. To recover this loss, the overlapping partial fields-of-view are merged via utilizing the continuity and positivity of the desired image. In this work, an image reconstruction technique that merges the partial fields-of-view while optimizing the signal-to-noise ratio is proposed. Accordingly, each partial field-of-view must be weighted by the square of the position-dependent scanning speed. Via extensive simulations at various overlap percentages and signal-to-noise ratios, this work demonstrates that the proposed method overcomes the vertical line artifacts caused by the standard MPI reconstruction techniques and improves image quality.
Open Access
Near IR absorbing bodipy-functionalized SPIONs: a potential magnetic nanoplatform for diagnosis and therapy
(De Gruyter, 2014) Ertem, E.; Bekdemir, A.; Atilgan, A.; Akkaya, E. U.
Photodynamic therapy (PDT), especially with the recent advances in photosensitizer (PS) design, has already been established as a noninvasive technique for cancer treatment. Recently, near-IR-based absorbing PSs that have a rising potency to implement light-triggered tumor ablation have attracted much attention since near-IR light in the 650-850 nm range penetrates more deeply in tissues. Up to now, numerous nanomaterials tailored to suitable sizes have been studied for effective delivery of PSs. In this study, four different types of Bodipy-based PSs were covalently attached to magnetic resonance imaging (MRI) active, biocompatible, and nontoxic nanocarriers and generation of singlet oxygen capabilities were evaluated. It was demonstrated that these core-shell nanoparticles are promising delivery vehicles of PSs for use in diagnosis and therapy.
Open Access
A new class of cubic SPIONs as a dual-mode T1 and T2 contrast agent for MRI
(Elsevier, 2018) Alipour, Akbar; Soran-Erdem, Zeliha; Utkur, Mustafa; Sharma, Vijay Kumar; Algın, Oktay; Sarıtaş, Emine Ülkü; Demir, Hilmi Volkan
Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as a robust negative contrast agent on conventional MRI. In this study, we (a) synthesized a new class of cubic SPIONs as a dual-mode contrast agent in MRI and (b) showed the in-vivo feasibility of these nanaoparticles as a simultaneous positive and negative contrast agent. Relaxation properties and contrast enhancement analysis of the synthesized SPIONs with two different shapes (cubic vs. spherical) and three different sizes 7 nm, 11 nm, and 14 nm were investigated to evaluate contrast enhancement in-vitro. In-vivo MRI experiments were performed on a 3T MR scanner, where a healthy anesthetized rat was imaged before, and from 20 to 80 min after intravenous injection of 1 mg/kg of contrast agent. Representative transmission electron microscopy (TEM) images of the synthesized nanoparticles reveal that the particles are well dispersed in a solvent and do not aggregate. The in-vitro relaxivity and contrast enhancement analysis show that, among all six SPIONs tested, 11-nm cubic SPIONs possess optimal molar relaxivities and contrast enhancement values, which can shorten the spin-lattice and spin-spin relaxation times, simultaneously. No noticeable toxicity is observed during in-vitro cytotoxicity analysis. In-vivo T1-and T2-weighted acquisitions at 60-min post-injection of 11-nm cubic SPIONs result in 64% and 48% contrast enhancement on the T1-and T2-weighted images, respectively. By controlling the shape and size of SPIONs, we have introduced a new class of cubic SPIONs as a synergistic (dual-mode) MRI contrast agent. 11-nm cubic SPIONs with smaller size and high positive and negative contrast enhancements were selected as a promising candidate for dual-mode contrast agent. Our proof-of-concept MRI experiments on rat demonstrate the in-vivo dual-mode contrast enhancement feasibility of these nanoparticles.
Open Access
Peptide functionalized superparamagnetic iron oxide nanoparticles as MRI contrast agents
(The Royal Society of Chemistry, 2011) Sulek, S.; Mammadov, B.; Mahcicek, D. I.; Sozeri, H.; Atalar, Ergin; Tekinay, A. B.; Güler, Mustafa O.
Magnetic resonance imaging (MRI) attracts great attention in cellular and molecular imaging due to its non-invasive and multidimensional tomographic capabilities. Development of new contrast agents is necessary to enhance the MRI signal in tissues of interest. Superparamagnetic iron oxide nanoparticles (SPIONs) are used as contrast agents for signal enhancement as they have revealed extraordinary magnetic properties at the nanometre size and their toxicity level is very low compared to other commercial contrast agents. In this study, we developed a new method to functionalize the surface of SPIONs. Peptide amphiphile molecules are used to coat SPIONs non-covalently to provide water solubility and to enhance biocompatibility. Superparamagnetic properties of the peptide-SPION complexes and their ability as contrast agents are demonstrated. In vitro cell culture experiments reveal that the peptide-SPION complexes are biocompatible and are localized around the cells due to their peptide coating.