{"id":986,"date":"2019-02-05T15:02:47","date_gmt":"2019-02-05T14:02:47","guid":{"rendered":"http:\/\/www.vincent.org.rs\/en\/?page_id=986"},"modified":"2019-03-14T12:45:53","modified_gmt":"2019-03-14T11:45:53","slug":"the-tumor-immune-microenvironment-is-reshaped-after-systemic-exposure-to-magnetic-iron-oxide-nanoparticles-a-study-in-mouse-models-of-breast-cancer","status":"publish","type":"page","link":"http:\/\/www.vincent.org.rs\/en\/r_ivkov_abstract\/","title":{"rendered":"The tumor immune microenvironment is reshaped after systemic exposure to magnetic iron oxide nanoparticles: A study in mouse models of breast cancer"},"content":{"rendered":"\n<p style=\"text-align:center\">Preethi Korangath, James Barnett, Anirudh Sharma, Elizabeth Henderson, Jacqueline Stewart, Shu-Han Yu, Sri Kamal Kandala, Chun-Ting Yang, Mohammad Hedayati, Todd Armstrong, Elizabeth Jaffee, Cordula Gruettner, Xian C Zhou, Wei Fu, Chen Hu, Saraswati Sukumar, Brian W Simons and <a href=\"http:\/\/www.vincent.org.rs\/en\/r_ivkov\/\">Robert Ivkov<\/a><sup>1<\/sup> <\/p>\n\n\n\n<p> <em><sup>1<\/sup>Johns Hopkins University School of Medicine, Baltimore, USA<\/em><\/p>\n\n\n\n<p>The factors that\ninfluence selective accumulation of nanoparticles into solid tumors remain an\narea of intense interest. Five tumorigenic human breast cancer cell lines with\nvarying HER2 status were used to grow orthotopic mammary tumors in nude and\nNOD\/SCID gamma (NSG) mice. A human HER2 overexpressing (huHER2) transgenic\nmouse (Genentech) was used to develop a syngeneic allograft model that was\nimplanted across FVB\/N (immune competent), nude, and NSG mice for comparative\nstudies of tumor retention of nanoparticles. Starch-coated bionized nanoferrite\n(BNF) nanoparticles labeled with trastuzumab (BNF-HER), unlabeled (BNF-Plain),\nor PBS (control) were injected into tail veins of mice when tumors had a\nmeasured volume of ~150 mm<sup>3<\/sup>. 24 hrs following intravenous injection,\nmice were sacrificed and tissues harvested for analysis.&nbsp;<\/p>\n\n\n\n<p>We demonstrate\nusing inductively coupled plasma mass spectrometry and extensive\nhistophathology analysis that unlabeled starch-coated magnetic iron oxide\nnanoparticles showed little accumulation in tumors regardless of tumor model or\nhost strain. Surprisingly, retention of BNF-HER nanoparticles was evident\nacross all tumor models, with little variation among the models. Further\nanalysis showed that retention of the antibody-labeled counterpart in tumors\ndepended more on immune status of the host than on presence of the target\nantigen.&nbsp;<em><\/em><\/p>\n\n\n\n<p><em>In vitro<\/em>, a T<sub>H<\/sub>1-type activation of murine\nmacrophages and neutrophils led to preferential uptake of antibody-conjugated\nnanoparticles, suggesting nanoparticle retention in tumors was determined by an\ninflammatory tumor-microenvironment. In the immune competent huHER2 allograft\nmodel, accumulation of plain nanoparticles was minimal as observed in human\nxenograft models. Conversely, retention of BNF-HER nanoparticles in FVB\/N mice\nbearing huHER2 tumors was dramatically higher than in nude or NSG mice bearing\nthis tumor, with tumor retention occurring primarily in tumor-associated\ndendritic cells, neutrophils, monocytes, and macrophages as determined by\nmagnetically sorted flow cytometry. An intact immune system with\ncompetent&nbsp;T<sub>H<\/sub>1 activation displayed preferential retention of\nantibody-labeled BNF nanoparticles.<\/p>\n\n\n\n<p>Systemic exposure\nof immune intact allograft (implanted) huHER2 models to either plain or\ntrastuzumab-labeled BNF nanoparticles delayed tumor growth and caused CD8<sup>+<\/sup>&nbsp;T\ncell infiltration fourteen days after injection.<\/p>\n\n\n\n<p>These findings\ndemonstrate that the immune microenvironment of solid-cancer tumors can be a\ndominant factor that determines nanoparticle retention in tumors, and that\nsystemic exposure to nanoparticles has potential to initiate systemic immune\nresponses leading to adaptive immune-mediated tumor growth inhibition. \n\nOur\nresults show that nanoparticle constructs offer anti-cancer immune-modulating\npotential that can be exploited for cancer immune therapy.\n\n\n\n<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Preethi Korangath, James Barnett, Anirudh Sharma, Elizabeth Henderson, Jacqueline Stewart, Shu-Han Yu, Sri Kamal Kandala, Chun-Ting Yang, Mohammad Hedayati, Todd Armstrong, Elizabeth Jaffee, Cordula Gruettner, Xian C Zhou, Wei Fu, Chen Hu, Saraswati Sukumar, Brian W Simons and Robert Ivkov1 1Johns Hopkins University School of Medicine, Baltimore, USA The factors that influence selective accumulation of [&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\/986"}],"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=986"}],"version-history":[{"count":3,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages\/986\/revisions"}],"predecessor-version":[{"id":1196,"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/pages\/986\/revisions\/1196"}],"wp:attachment":[{"href":"http:\/\/www.vincent.org.rs\/en\/wp-json\/wp\/v2\/media?parent=986"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}