{"id":980,"date":"2019-02-05T14:58:28","date_gmt":"2019-02-05T13:58:28","guid":{"rendered":"http:\/\/www.vincent.org.rs\/en\/?page_id=980"},"modified":"2019-02-25T09:14:40","modified_gmt":"2019-02-25T08:14:40","slug":"monocore-or-multicore-iron-oxide-nanoparticles-synthesized-in-polyols-and-coated-with-a-thermosensitive-cell-penetrating-peptide","status":"publish","type":"page","link":"http:\/\/www.vincent.org.rs\/en\/o_sandre_abstract\/","title":{"rendered":"Monocore or multicore iron oxide nanoparticles synthesized in polyols and coated with a thermosensitive cell-penetrating peptide"},"content":{"rendered":"\n<p><strong><a href=\"http:\/\/www.vincent.org.rs\/en\/o_sandre\/\">Oliver Sandre<\/a><\/strong><sup>1<\/sup>, Gauvin H\u00e9mery<sup>1<\/sup>, Emmanuel Ibarboure<sup>1<\/sup>, Elisabeth Garanger<sup>1<\/sup>, S\u00e9bastien Lecommandoux<sup>1<\/sup>, Pauline Jeanjean<sup>2<\/sup>, Coralie Genevois<sup>2<\/sup>, Franck Couillaud<sup>2<\/sup>, Sabrina Lacomme<sup>3<\/sup>, Etienne Gontier<sup>3<\/sup>, Ashutosh Chilkoti<sup>4<\/sup><\/p>\n\n\n\n<p><em>1 LCPO\nUMR5629 Univ Bordeaux, CNRS, Bordeaux INP, ENSCBP, Pessac, France<\/em><\/p>\n\n\n\n<p><em><sup>2<\/sup><\/em><em> IMOTION\nEA7435 Univ Bordeaux, Bordeaux, France.<\/em><\/p>\n\n\n\n<p><em><sup>3<\/sup> BIC UMS3420 Univ Bordeaux, CNRS, Inserm, Bordeaux, France.<\/em><\/p>\n\n\n\n<p><em><sup>4 <\/sup>Biomedical Engineering, Duke University, Durham, NC, United States.<\/em><\/p>\n\n\n\n<p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nThis communication reports the grafting onto\niron oxide nanoparticles (IONPs) of recombinant polypeptides made of di-block\nelastin-like peptide (ELP<sub>40-60<\/sub>) and cell-penetrating peptide (Tat)\nsequence.<a href=\"#_ftn1\"><strong>[1]<\/strong><\/a>The ELP<sub>40<\/sub> block is\nthermosensitive and undergoes a water de-swelling transition at a critical\ntemperature around 42 \u00b0C in solution, the ELP<sub>60<\/sub> block is hydrophilic\nand provides colloidal stability to the resulting \u03b3-Fe<sub>2<\/sub>O<sub>3<\/sub>@ELP<sub>40-60<\/sub>-Tat\ncore-shell IONPs. Magnetic IONPs were synthesized by a polyol pathway with\neither monocore (nanospheres) or multi-core (nanoflowers) morphology, narrow\nsize-dispersity and suitable heating efficiency under an alternating magnetic\nfield (AMF).<a href=\"#_ftn2\"><strong>[2]<\/strong><\/a>\nThe bio-functionalization of these IONPs with the di-block ELP<sub>40-60<\/sub>-Tat\nwas achieved by a convergent strategy through strong coordination bonding of a\nphosphonate group introduced near the N-terminus of the polypeptide. To the\nbest of our knowledge, this is the first report on a thermosensitive ELP<sub>m-n<\/sub>\npolypeptide brush grafting onto magnetic IONPs. Large temperature variations of\nthe sample (up to 30 \u00b0C) could be obtained in a few minutes by applying an AMF.\nFast size changes of the magnetic core-thermosensitive shell nanoparticles were\nmeasured by <em>in situ <\/em>dynamic\nlight-scattering (DLS) while the AMF was on. Variations of the hydrodynamic\nsize were compared to the classical polymer brush model revised for the highly\ncurved surface of nanoparticles. Cellular internalization and toxicity assays\nwere performed on a glioblastoma (U87) human cancer cell line in view of\napplications for drug delivery activated magnetically. Superior cellular uptake\nwas observed <em>in vitro <\/em>for multicore\nIONPs compared to monocore IONPs (for the same PEG coating),<a href=\"#_ftn3\"><strong>[3]<\/strong><\/a>\nand for IONPs@ELP<sub>40-60<\/sub>-Tat peptide-grafted nanoparticles compared to\nIONPs@PEG controls prepared from the same (spherical) cores. The\ninternalization pathway in lysosomes was monitored by electron microscopy on\nmicrotomes and confocal optical microscopy on live cells. Cellular toxicity\nafter AMF application with these core-shell IONPs was ascribed to lysosomal\nmembrane rupture and leakage into the cytosol. The intra-cellular fate of such\nIONPs, from their internalization to the effect of an AMF application,\nvalidates the use of thermosensitive peptide brushes on IONPs as drug delivery\nsystems, addressing lysosomal compartments and triggering leakage of their\ncontent by external AMF application. Preliminary <em>in vivo<\/em> experiments evidenced the positive effect of the Tat\npeptide end-sequence compared to the PEG brush control on the bio-distribution,\nwith similar contents in the liver and in U87 model tumor in mice. Long term\nfate (after 48 h) is discussed in view of the cell division with equal sharing of\nthe magnetically loaded lysosomes among daughter cells, possibly envisioning\nthe successive application of magnetic hyperthermia on time scales superior to\nthe cellular life cycle\n\n<br \/><\/p>\n\n\n\n<hr class=\"wp-block-separator\"\/>\n\n\n\n<p><a href=\"#_ftnref1\">[1]<\/a> E Garanger, S\nMacEwan, O Sandre, A Br\u00fblet, L Bataille, A Chilkoti, S Lecommandoux, <em>Macromol.<\/em> 2015, 48, 6617<\/p>\n\n\n\n<p><a href=\"#_ftnref2\">[2]<\/a> G Hemery, A\nKeyes, E Garaio, I Rodrigo, J A Garcia, F Plazaola, E Garanger, O Sandre, <em>Inorg. <\/em><em>Chem.<\/em> 2017, 56, 8232<\/p>\n\n\n\n<p><a href=\"#_ftnref3\">[3]<\/a> G Hemery, C Genevois, F\nCouillaud, S Lacomme, E Gontier, E Ibarboure, S Lecommandoux, E Garanger, O\nSandre, <em>Molecular Systems Design &amp;\nEngineering<\/em> 2017, 2 629<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Oliver Sandre1, Gauvin H\u00e9mery1, Emmanuel Ibarboure1, Elisabeth Garanger1, S\u00e9bastien Lecommandoux1, Pauline Jeanjean2, Coralie Genevois2, Franck Couillaud2, Sabrina Lacomme3, Etienne Gontier3, Ashutosh Chilkoti4 1 LCPO UMR5629 Univ Bordeaux, CNRS, Bordeaux INP, ENSCBP, Pessac, France 2 IMOTION EA7435 Univ Bordeaux, Bordeaux, France. 3 BIC UMS3420 Univ Bordeaux, CNRS, Inserm, Bordeaux, France. 4 Biomedical Engineering, Duke University, Durham, [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages\/980"}],"collection":[{"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/comments?post=980"}],"version-history":[{"count":4,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages\/980\/revisions"}],"predecessor-version":[{"id":1158,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages\/980\/revisions\/1158"}],"wp:attachment":[{"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/media?parent=980"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}