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      Hyaluronic Acid-Modified Magnetic Iron Oxide Nanoparticles for MR Imaging of Surgically Induced Endometriosis Model in Rats

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          Abstract

          Endometriosis is defined as the presence of endometrial tissue outside the uterine, which may affect nearly 60% of women in reproductive age. Deep infiltrating endometriosis (DIE) defined as an endometriotic lesion penetrating into the retroperitoneal space or the wall of the pelvic organs to a depth of at least 5 mm represents the most diagnostic challenge. Herein, we reported the use of hyaluronic acid (HA)-modified magnetic iron oxide nanoparticles (HA-Fe 3O 4 NPs) for magnetic resonance (MR) imaging of endometriotic lesions in the rodent model. Sixteen endometriotic lesions were surgically induced in eight rats by autologous transplantation. Four weeks after lesion induction, three rats were scanned via MR imaging after tail vein injection of the HA-Fe 3O 4 NPs. Accordingly, the remaining five mice were sacrificed in the corresponding time points. The ectopic uterine tissues (EUTs) were confirmed by histological analysis. Quantification of Fe in the EUT was also performed by inductively coupled plasma-optical emission spectroscopy. Our results showed that by using the HA-Fe 3O 4 NPs, the EUTs were able to be visualized via T 2-weighted MR imaging at 2 hours post injection, corroborating the Prussian blue staining results. The developed HA-Fe3O4 NPs could be used as negative contrast agents for sensitively detecting endometriosis in a mouse model and may be applied for future hyperthermia treatment of endometriosis.

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          Most cited references33

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          Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents.

          Various magnetic nanoparticles have been extensively investigated as novel magnetic resonance imaging (MRI) contrast agents owing to their unique characteristics, including efficient contrast effects, biocompatibility, and versatile surface functionalization capability. Nanoparticles with high relaxivity are very desirable because they would increase the accuracy of MRI. Recent progress in nanotechnology enables fine control of the size, crystal structure, and surface properties of iron oxide nanoparticles. In this tutorial review, we discuss how MRI contrast effects can be improved by controlling the size, composition, doping, assembly, and surface properties of iron-oxide-based nanoparticles.
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            Multifunctional magnetic nanoparticles for targeted imaging and therapy.

            Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials.
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              In vivo biodistribution and clearance studies using multimodal organically modified silica nanoparticles.

              Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with (124)I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                10 April 2014
                : 9
                : 4
                : e94718
                Affiliations
                [1 ]Department of Radiology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, PR China
                [2 ]College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, PR China
                Brandeis University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HZ GZ MS XS. Performed the experiments: HZ JL WS YH. Analyzed the data: HZ JL. Contributed reagents/materials/analysis tools: HZ JL WS YH. Wrote the paper: HZ JL. Revised the paper: XS.

                Article
                PONE-D-14-06065
                10.1371/journal.pone.0094718
                3983238
                24722347
                f412833f-56f4-4bc7-b858-31d0248bcee4
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 February 2014
                : 18 March 2014
                Page count
                Pages: 6
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology and Life Sciences
                Biotechnology
                Biomaterials
                Engineering and Technology
                Nanotechnology
                Nanomaterials
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Radiology and Imaging
                Physical Sciences
                Materials Science

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