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      Magnetic nanoparticles: a strategy to target the choroidal layer in the posterior segment of the eye

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          Abstract

          Despite the higher rate of blindness due to population aging, minimally invasive and selective drug delivery to the eye still remains an open challenge, especially in the posterior segment. The retina, the retinal pigment epithelium (RPE) and the choroid are posterior segment cell layers, which may be affected by several diseases. In particular, damages to the choroid are associated with poor prognosis in the most severe pathologies. A drug delivery approach, able to target the choroid, is still missing. Recently, we demonstrated that intravitreally injected magnetic nanoparticles (MNP) are able to rapidly and persistently localise within the RPE in an autonomous manner. In this work we functionalised the MNP surface with the vascular endothelial growth factor, a bioactive molecule capable of transcytosis from the RPE towards more posterior layers. Such functionalisation successfully addressed the MNPs to the choroid, while MNP functionalised with a control polypeptide (poly-L-lysine) showed the same localisation pattern of the naked MNP particles. These data suggest that the combination of MNP with different bioactive molecules could represent a powerful strategy for cell-specific targeting of the eye posterior segment.

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          Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking

          Stem cells hold great promise for the treatment of multiple human diseases and disorders. Tracking and monitoring of stem cells in vivo after transplantation can supply important information for determining the efficacy of stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be the most effective and safest non-invasive technique for stem cell tracking in living bodies. Commercial superparamagnetic iron oxide nanoparticles (SPIONs) in the aid of transfection agents (TAs) have been applied to labeling stem cells. However, owing to the potential toxicity of TAs, more attentions have been paid to develop novel SPIONs with specific surface coating or functional moieties which facilitate effective cell internalization in the absence of TAs. This review aims to summarize the recent progress in the design and preparation of SPIONs as cellular MRI probes, to discuss their applications and current problems facing in stem cell labeling and tracking, and to offer perspectives and solutions for the future development of SPIONs in this field.
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            Polarized vascular endothelial growth factor secretion by human retinal pigment epithelium and localization of vascular endothelial growth factor receptors on the inner choriocapillaris. Evidence for a trophic paracrine relation.

            The retinal pigment epithelium (RPE) maintains the choriocapillaris (CC) in the normal eye and is involved in the pathogenesis of choroidal neovascularization in age-related macular degeneration. Vascular endothelial growth factor-A (VEGF) is produced by differentiated human RPE cells in vitro and in vivo and may be involved in paracrine signaling between the RPE and the CC. We investigated whether there is a polarized secretion of VEGF by RPE cells in vitro. Also, the localization of VEGF receptors in the human retina was investigated. We observed that highly differentiated human RPE cells, cultured on transwell filters in normoxic conditions, produced two- to sevenfold more VEGF toward their basolateral side as compared to the apical side. In hypoxic conditions, VEGF-A secretion increased to the basal side only, resulting in a three- to 10-fold higher basolateral secretion. By immunohistochemistry in 30 human eyes and in two cynomolgus monkey eyes, KDR (VEGFR-2) and flt-4 (VEGFR-3) were preferentially localized at the side of the CC endothelium facing the RPE cell layer, whereas flt-1 (VEGFR-1) was found on the inner CC and on other choroidal vessels. Our results indicate that RPE secretes VEGF toward its basal side where its receptor KDR is located on the adjacent CC endothelium, suggesting a role of VEGF in a paracrine relation, possibly in cooperation with flt-4 and its ligand. This can explain the known trophic function of the RPE in the maintenance of the CC and its fenestrated permeable phenotype and points to a role for VEGF in normal eye functioning. Up-regulated basolateral VEGF secretion by RPE in hypoxia or loss of polarity of VEGF production may play a role in the pathogenesis of choroidal neovascularization.
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              Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications.

              Superparamagnetic iron oxide nanoparticles (SPION) based magnetic resonance imaging (MRI) is a powerful non-invasive tool in biomedical imaging, clinical diagnosis and therapy. In this review, the physicochemical properties of SPION and their in vivo performance were thoroughly discussed, also covering how surface engineering will prolong the circulation time and overcome biological barriers at organ, tissue, and cellular levels. Clinical applications and future potentials of SPION based MR imaging in cancer, cardiovascular, and inflammation diseases were addressed. Targeting mechanisms of SPION in both research and clinical use were summarized for better understanding of their performance. Addition of new targeting mechanisms to clinically approved SPION will bring opportunities to discover early diseases at cellular and molecular levels, and to track MRI-visible drug carriers. Clinical trial information related to SPION on Clinicaltrials.gov was summarized mainly based on their disease categories, therapeutic applications and clinical trial stages. It gives us a brief outlook of their clinical applications in the near future. Copyright © 2014 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                03 March 2017
                2017
                : 7
                : 43092
                Affiliations
                [1 ]Department of Biology, Università di Pisa , 56127, Pisa, Italy
                [2 ]Department of Chemistry and Industrial Chemistry, Università di Pisa , 56124, Pisa, Italy
                [3 ]Institute of Life Science, Scuola Superiore Sant’Anna , 56127, Pisa, Italy
                Author notes
                Article
                srep43092
                10.1038/srep43092
                5335660
                28256525
                76c54612-4772-4983-b1a5-c0cdc1a305dd
                Copyright © 2017, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 26 July 2016
                : 19 January 2017
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