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This project was supported in part by appointments to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. \n Funding text 2: This project was supported in part by appointments to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.", "unhandledTickets" : 0, "deleted" : false, "lastRefresh" : "2024-01-23T11:24:38.587+0000", "lastModified" : "2019-05-31T07:24:50.522+0000", "created" : "2019-05-23T14:50:50.425+0000", "creator" : { "otype" : "Author", "mtid" : 10010387, "link" : "/api/author/10010387", "label" : "Mihály Judith (IR és Raman spektroszkópia, biofizika)", 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"publishedYear" : 2019, "abstractText" : "Different nanomaterials are under development for various biomedical applications in which nanoparticles contact blood and vasculature. Therefore, investigating the interactions between nanomaterials and vascular endothelial cells (ECs) is of great importance. Here, we show the effects of polyamidoamine (PAMAM) dendrimers of two different sizes, generation 2 (G2; approximately 3 nm diameter) and generation 7 (G7; 9 nm), with neutral (OH-terminated), anionic (COOH-terminated), and cationic (NH2-terminated) surface modifications on cultured human umbilical vein ECs (HUVECs). We found that only cationic dendrimers (5-100 mu g/mL G7-NH2 and 100 mu g/mL G2-NH2) and not anionic or neutral dendrimers were cytotoxic to HUVECs. In addition, cationic dendrimers at low concentrations (5 mu g/mL) markedly increased the HUVEC surface expression of the proinflammatory activation marker ICAM-1 and phosphatidylserine (PS). Both G2-NH2 and G7-NH2 dendrimers caused g1 arrest, but only G7-NH2 dendrimers induced significant HUVEC apoptosis. G7-NH2 interacted strongly with HUVEC plasma membranes and mitochondrial membranes, and phospholipid vesicles containing G7-NH2 formed, which resulted in extensive plasma membrane blebbing and disintegration. Furthermore, flow cytometric analysis showed that G7-NH2-treated HUVECs released large numbers of extracellular vesicles (EVs) positive for CD105 and PS. A notable population of EVs positive for the mitochondrial marker TOM20 but negative for the autophagosome marker LC3 was found. In summary, large cationic PAMAM dendrimers (G7-NH2) showed both proinflammatory and proapoptotic effects in ECs; at high dendrimer concentrations, these effects were accompanied by necrotic cytotoxicity. G7-NH2 caused plasma and mitochondrial membrane disintegration and the release of EVs, including EVs of mitochondrial origin that were not associated with mitophagy.", "subjects" : [ { "otype" : "Classification", "mtid" : 12125, "link" : "/api/classification/12125", "label" : "Általános orvostudomány", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 11077, "link" : "/api/classification/11077", "label" : "Nanotechnológia", "published" : true, "snippet" : true } ], "keywords" : [ { "otype" : "Keyword", "mtid" : 64, "link" : "/api/keyword/64", "label" : "Inflammation", "published" : true, "oldId" : 64, "snippet" : true }, { "otype" : "Keyword", "mtid" : 300, "link" : "/api/keyword/300", "label" : "APOPTOSIS", "published" : true, "oldId" : 300, "snippet" : true }, { "otype" : "Keyword", "mtid" : 5016, "link" : "/api/keyword/5016", "label" : "Mitochondria", "published" : true, "oldId" : 5016, "snippet" : true }, { "otype" : "Keyword", "mtid" : 7722, "link" : "/api/keyword/7722", "label" : "Flow Cytometry", "published" : true, "oldId" : 7722, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1253071, "link" : "/api/keyword/1253071", "label" : "Extracellular vesicles", "published" : true, "oldId" : 1253071, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1517386, "link" : "/api/keyword/1517386", "label" : "Nanoparticle toxicity", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2019, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : null, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2024-01-23", "oaFree" : false, "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 2, "citedCount" : 2, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10906839, "link" : "/api/sjrrating/10906839", "label" : "sjr:D1 (2019) Scopus - Toxicology NANOTOXICOLOGY 1743-5390", "listPos" : 10, "rankValue" : 0.1, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 3005, "link" : "/api/classificationexternal/3005", "label" : "Scopus - Toxicology", "published" : true, "oldId" : 3005, "snippet" : true }, "ranking" : "D1", "calculation" : "DIRECT", "published" : true, "snippet" : true } ], "ratingsForSort" : "D1", "hasCitationDuplums" : false, "userChangeableUntil" : "2019-08-29T07:24:50.253+0000", "directInstitutesForSort" : "", "ownerAuthorCount" : 10, "ownerInstituteCount" : 49, "directInstituteCount" : 0, "authorCount" : 5, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/30685883", "label" : "Patel Mehulkumar et al. 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