{"id":275,"date":"2017-10-31T16:26:12","date_gmt":"2017-10-31T20:26:12","guid":{"rendered":"http:\/\/sites.nd.edu\/pdnano\/?p=275"},"modified":"2024-01-11T11:45:58","modified_gmt":"2024-01-11T15:45:58","slug":"ccytocompatibility-of-hafnium-oxide-nanoparticle-imaging-probes-prepared-using-a-novel-templated-synthesis","status":"publish","type":"post","link":"https:\/\/sites.nd.edu\/pdnano\/?p=275","title":{"rendered":"Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis"},"content":{"rendered":"<div id=\"attachment_276\" style=\"width: 190px\" class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-276\" class=\"wp-image-276 size-medium\" src=\"http:\/\/sites.nd.edu\/pdnano\/files\/2017\/10\/Hafnia-graphic-180x300.png\" alt=\"\" width=\"180\" height=\"300\" srcset=\"https:\/\/sites.nd.edu\/pdnano\/files\/2017\/10\/Hafnia-graphic-180x300.png 180w, https:\/\/sites.nd.edu\/pdnano\/files\/2017\/10\/Hafnia-graphic.png 450w\" sizes=\"auto, (max-width: 180px) 100vw, 180px\" \/><p id=\"caption-attachment-276\" class=\"wp-caption-text\">Figure 1. (A) TEM micrograph of an individual HfOR2R NP. Scale bar = 5 nm. (B) X-ray radiograph and (C) fluorescence of CY5-HfOR2R NPs in an Eppendorf tube. (D) Hydrodynamic diameter of HfOR2R NPs and CY5-HfOR2R NPs in water over 24 h. (E,F) Live\/Dead assay confirmed &gt;99% viability and (G,H) confocal microscopy confirmed cellular uptake of CY5-HfOR2R NPs in (E,G) HeLa and (F,H) THP-1 cells. Scale bars = 20 \uf06dm<\/p><\/div>\n<p>This work will be presented at MRS 2018 and at SFB 2018<\/p>\n<p><strong>Statement of Purpose<\/strong>: Hafnium oxide (HfO<sub>2<\/sub>) with a k-edge of 50 keV is being explored as a clinical X-ray contrast agent. HfO<sub>2 <\/sub>NPs are also in clinical trials as radiosensitizers that induce immune action against tumor sites. \u00a0\u00a0However, the unpredictable stability of commercially available HfO<sub>2 <\/sub>makes it hard to predict their pharmacokinetics and their size range of <sub>(<\/sub>(50-100 nm) results in zero clearance from an <em>in vivo<\/em> system. Therefore, in this study we have executed a modular approach for the design and scalable synthesis of novel, non-sintered, 4-8 nm metal oxide nanoparticles (e.g. Hafnium oxide, Gadolinium oxide) with 40-60 fold higher X-ray attenuation cross-sections than the NPs diameter. Contrast-enhanced computed tomography (CT) and spectral (color) X-ray CT with the aid of these new class of probes have the potential to enable targeted image guided therapeutics with CT as a lower cost and higher resolution alternative to PET and MRI.<\/p>\n<p><strong>Results<\/strong>: We achieved &gt;95% efficient conversion of the amorphous seed NPs to crystalline orthorhombic-HfO<sub>2<\/sub>\u00a0NPs. HfO<sub>2<\/sub>\u00a0NPswere ~4-5\u00a0nm in diameter (Fig.\u00a01A) and formed non-sintered flocculants, 220-290\u00a0nm in diameter. As-prepared CY5-HfO<sub>2<\/sub>\u00a0NPs\u00a0exhibited simultaneous X-ray contrast and fluorescence in multispectral imaging (Fig.\u00a0B,C). Both HfO<sub>2<\/sub>\u00a0and CY5-HfO<sub>2<\/sub>\u00a0NPs\u00a0remained well-dispersed over 24\u00a0h (Fig.\u00a01D). The measured zeta potential was -13 to -16\u00a0mV. Encapsulating the HfO<sub>2<\/sub>\u00a0NPs\u00a0in a SiO<sub>2<\/sub>\u00a0shell reduced the hydrodynamic diameter to ~30\u00a0nm and inhibited the formation of flocculants. MTT and Live\/Dead assays confirmed that the HfO<sub>2<\/sub>\u00a0NPs were neither cytotoxic nor pro-inflammatory (Fig.\u00a01E,F). Confocal microscopy confirmed highly efficient uptake of Cy5-HfO<sub>2<\/sub>\u00a0NPs by HeLa cells and THP-1 cells (Fig.\u00a01G,H).<\/p>\n<p><strong>Conclusion<\/strong>: HfO<sub>2<\/sub>\u00a0NPs were prepared using a novel templated synthesis resulting in crystalline NPs, ~4-5\u00a0nm in diameter, which flocculate into 220-290\u00a0nm clusters. Therefore, these NPs are anticipated to provide both long blood circulation and eventual renal clearance through phagocytic breakdown after delivery as radiographic imaging probe or radiosensitizer.<\/p>\n<p><strong>Acknowledgments<\/strong>: NSF DMR-1309587, DAAD PPP, Notre Dame GCI, Walther Cancer Foundation, ND<em>nano<\/em>.<\/p>\n<p><strong>Contributors:<\/strong>\u00a0 Prakash D. Nallathamby,<sup>1<\/sup> Viktoriya Sokolova,<sup>2<\/sup> Oleg Prymak,<sup>2<\/sup> Matthias Epple<sup>2<\/sup> and Ryan K. Roeder <sup>1<\/sup><\/p>\n<p><sup>1<\/sup>University of Notre Dame<\/p>\n<p><sup>2<\/sup>University of Duisburg-Essen<\/p>\n","protected":false},"excerpt":{"rendered":"<p>This work will be presented at MRS 2018 and at SFB 2018 Statement of Purpose: Hafnium oxide (HfO2) with a k-edge of 50 keV is being explored as a clinical X-ray contrast agent. HfO2 NPs are also in clinical trials as radiosensitizers that induce immune action against tumor sites. \u00a0\u00a0However, the unpredictable stability of commercially &hellip; <\/p>\n<p><a class=\"more-link block-button\" href=\"https:\/\/sites.nd.edu\/pdnano\/?p=275\">Continue reading &raquo;<\/a><\/p>\n","protected":false},"author":2672,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":true,"template":"","format":"standard","meta":{"footnotes":""},"categories":[405093,259656,269984,259341],"tags":[],"class_list":["post-275","post","type-post","status-publish","format-standard","hentry","category-berthiaume-institute-for-precision-health","category-biomedical-imaging","category-conference-abstracts","category-upcoming-manuscripts"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis - Nallathamby Laboratory<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/sites.nd.edu\/pdnano\/?p=275\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis - Nallathamby Laboratory\" \/>\n<meta property=\"og:description\" content=\"This work will be presented at MRS 2018 and at SFB 2018 Statement of Purpose: Hafnium oxide (HfO2) with a k-edge of 50 keV is being explored as a clinical X-ray contrast agent. HfO2 NPs are also in clinical trials as radiosensitizers that induce immune action against tumor sites. \u00a0\u00a0However, the unpredictable stability of commercially &hellip; Continue reading &raquo;\" \/>\n<meta property=\"og:url\" content=\"https:\/\/sites.nd.edu\/pdnano\/?p=275\" \/>\n<meta property=\"og:site_name\" content=\"Nallathamby Laboratory\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/prakashdn\" \/>\n<meta property=\"article:published_time\" content=\"2017-10-31T20:26:12+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-01-11T15:45:58+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/sites.nd.edu\/pdnano\/files\/2017\/10\/Hafnia-graphic-180x300.png\" \/>\n<meta name=\"author\" content=\"Prakash\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@prakashdn\" \/>\n<meta name=\"twitter:site\" content=\"@prakashdn\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Prakash\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275\"},\"author\":{\"name\":\"Prakash\",\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/#\\\/schema\\\/person\\\/3bec2d9fbd957b23abd53a0a5445b4f0\"},\"headline\":\"Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis\",\"datePublished\":\"2017-10-31T20:26:12+00:00\",\"dateModified\":\"2024-01-11T15:45:58+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275\"},\"wordCount\":464,\"image\":{\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275#primaryimage\"},\"thumbnailUrl\":\"http:\\\/\\\/sites.nd.edu\\\/pdnano\\\/files\\\/2017\\\/10\\\/Hafnia-graphic-180x300.png\",\"articleSection\":[\"Berthiaume Institute for Precision Health\",\"Biomedical Imaging\",\"Conference abstracts\",\"Upcoming manuscripts\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275\",\"url\":\"https:\\\/\\\/sites.nd.edu\\\/pdnano\\\/?p=275\",\"name\":\"Cytocompatibility of Hafnium Oxide Nanoparticle Imaging Probes Prepared Using a Novel Templated Synthesis - 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