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We previously demonstrated that type 5 metabotropic glutamate receptor, mGluR5, is required to proliferate metastatic osteosarcoma cells. In this work, we delivered mGluR5 siRNAs in vitro using superparamagnetic iron oxide nanocages (IO-nanocages) as delivery vehicles and applied alternating magnetic fields (AMFs) to improve mGluR5 siRNAs release. We observed functional outcomes when mGluR5 expression is silenced in human and mouse osteosarcoma cell lines. The results elucidated that the mGluR5 siRNAs were successfully delivered by IO-nanocages and their release was enhanced by AMFs, leading to mGluR5 silencing. Moreover, we observed that the proliferation of both human and mouse osteosarcoma cells decreased significantly when mGluR5 expression was silenced in the cells. This novel magnetic siRNA delivery methodology was capable of silencing mGluR5 expression significantly in osteosarcoma cell lines under the AMFs, and our data suggested that this method can be further used in future clinical applications in cancer therapy.<\/jats:p>","DOI":"10.3390\/ijms23147944","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T05:37:53Z","timestamp":1658209073000},"page":"7944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Delivery of mGluR5 siRNAs by Iron Oxide Nanocages by Alternating Magnetic Fields for Blocking Proliferation of Metastatic Osteosarcoma Cells"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-8106","authenticated-orcid":false,"given":"Min A","family":"Kang","sequence":"first","affiliation":[{"name":"Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Department of Chemistry, Hunter College, City University of New York, 695 Park Ave., New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-4715","authenticated-orcid":false,"given":"Pooja P.","family":"Rao","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Department of Medical Laboratory Science, Hunter College, City University of New York, 425 East 25th Street, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsui","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Department of Chemistry, Hunter College, City University of New York, 695 Park Ave., New York, NY 10065, USA"},{"name":"Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Department of Biochemistry, Weill Cornell Medical College, 413 East 69th Street, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-695X","authenticated-orcid":false,"given":"Shahana S.","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Department of Medical Laboratory Science, Hunter College, City University of New York, 425 East 25th Street, New York, NY 10010, USA"},{"name":"Ph.D. Program in Biology, The Graduate Center of the City University of New York, 364 5th Ave., New York, NY 10016, USA"},{"name":"Brain Mind Research Institute, Weill Cornell Medical College, 413 East 69th Street, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"ref_1","first-page":"705","article-title":"Osteosarcoma: A review of diagnosis, management, and treatment strategies","volume":"8","author":"Geller","year":"2010","journal-title":"Clin. 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