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10.1021/acsnano.5b00428 http://scihub22266oqcxt.onion/10.1021/acsnano.5b00428 C4414893!4414893!25790730     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25790730&cmd=llinks): Failed to open stream: HTTP request failed! 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Characterizing the Interactions of Organic Nanoparticles with Renal Epithelial Cells in Vivo |pdf=|usr=}}{{25790730}} gab.com Text Characterizing the Interactions of Organic Nanoparticles with Renal Epithelial Cells in Vivo JO: ACS Nano http://www.kidney.de/pget.php?&tw=1&pmid=25790730 #FOAvip Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (< 10 nm), designed to be renally excreted. The active endocytic machinery of kidney proximal tubules avidly internalizes filtered proteins, which may also be the case for filtered nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose and time dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in dose dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression, and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function but changes in endocytosis mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available. Nanomaterials have enjoyed widespread use for different biomedical applications because they can be synthesized easily, adapted in modular fashion, used to exploit multivalency of attached affinity ligands for improved avidity,1 designed as smart sensors,2 designed to incorporate therapeutics (theranostics)3 and detected by multiple imaging techniques (multimodality imaging). While most therapeutic nanoparticles (NP) are designed in the 30?300 nm size range, imaging agents are often smaller. For example, dextran coated magnetic NP for MR imaging are often 30?50 nm, while other materials have been designed in the <10 nm range with the intention for them to be renally cleared.4,5 More recently, polymer-derived materials have also been synthesized in this size range6 as it became clear that they would offer unique advantages over larger materials. However, little is known about how highly specialized renal tubular cells process these small materials. Tubular cells encounter especially high local concentrations of such supersmall nanomaterials. While conventional hematoxylin and eosin (HE) stains done as part of regular toxicity studies are often normal, recent transmission electron microscopy (TEM) studies have revealed mitochondrial alterations in renal tubular epithelial cells up to 6 months after intravenous injection of quantum dots7. While metal based NPs represent a unique set of toxicity concerns, we set out to determine the effects of polymer based materials. We were particularly interested in a dextran coated type of material, given its similarity to an FDA approved preparation and effective macrophage targeting capabilities in vivo.8 Twit Text FOAVip Characterizing the Interactions of Organic Nanoparticles with Renal Epithelial Cells in Vivo ????ACS Nano http://www.kidney.de/pget.php?&tw=1&pmid=25790730 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25790730 #FOAvip English Wikipedia <ref>{{Cite pmid|25790730}}</ref> Characterizing the Interactions of Organic Nanoparticles with Renal Epithelial Cells in Vivo #MMPMID25790730 Nair AV; Keliher EJ; Core AB; Brown D; Weissleder R ACS Nano 2015[Apr]; 9 (4): 3641-53 PMID25790730show ga Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (< 10 nm), designed to be renally excreted. The active endocytic machinery of kidney proximal tubules avidly internalizes filtered proteins, which may also be the case for filtered nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose and time dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in dose dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression, and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function but changes in endocytosis mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available. Nanomaterials have enjoyed widespread use for different biomedical applications because they can be synthesized easily, adapted in modular fashion, used to exploit multivalency of attached affinity ligands for improved avidity,1 designed as smart sensors,2 designed to incorporate therapeutics (theranostics)3 and detected by multiple imaging techniques (multimodality imaging). While most therapeutic nanoparticles (NP) are designed in the 30?300 nm size range, imaging agents are often smaller. For example, dextran coated magnetic NP for MR imaging are often 30?50 nm, while other materials have been designed in the <10 nm range with the intention for them to be renally cleared.4,5 More recently, polymer-derived materials have also been synthesized in this size range6 as it became clear that they would offer unique advantages over larger materials. However, little is known about how highly specialized renal tubular cells process these small materials. Tubular cells encounter especially high local concentrations of such supersmall nanomaterials. While conventional hematoxylin and eosin (HE) stains done as part of regular toxicity studies are often normal, recent transmission electron microscopy (TEM) studies have revealed mitochondrial alterations in renal tubular epithelial cells up to 6 months after intravenous injection of quantum dots7. While metal based NPs represent a unique set of toxicity concerns, we set out to determine the effects of polymer based materials. We were particularly interested in a dextran coated type of material, given its similarity to an FDA approved preparation and effective macrophage targeting capabilities in vivo.8 äCharacterizing the Interactions of Organic Nanoparticles with Renal Ep(epmc).pdf DeepDyve Pubget Overpricing