Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo

Peter B Bartosik,1 Jessica E Fitzgerald,1 Mirna El Khatib,2 Mohammad A Yaseen,3 Sergei A Vinogradov,2 Mark Niedre1 1Department of Bioengineering, Northeastern University, Boston, MA, USA; 2Department of Biochemistry and Biophysics, Perelman School of Medicine and Department of Chemistry, School of A...

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Autores principales:	Bartosik PB, Fitzgerald JE, El Khatib M, Yaseen MA, Vinogradov SA, Niedre M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	in vivo flow cytometry upconverting nanoparticles phosphorescence Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/267d304675964fc78ddf5446e45f6639
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spelling	oai:doaj.org-article:267d304675964fc78ddf5446e45f66392021-12-02T05:21:47ZProspects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo1178-2013https://doaj.org/article/267d304675964fc78ddf5446e45f66392020-03-01T00:00:00Zhttps://www.dovepress.com/prospects-for-the-use-of-upconverting-nanoparticles-as-a-contrast-agen-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Peter B Bartosik,1 Jessica E Fitzgerald,1 Mirna El Khatib,2 Mohammad A Yaseen,3 Sergei A Vinogradov,2 Mark Niedre1 1Department of Bioengineering, Northeastern University, Boston, MA, USA; 2Department of Biochemistry and Biophysics, Perelman School of Medicine and Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; 3Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USACorrespondence: Mark Niedre Email m.niedre@neu.eduPurpose: We recently developed a new fluorescence-based technique called “diffuse in vivo flow cytometry” (DiFC) for enumerating rare circulating tumor cells (CTCs) directly in the bloodstream. Non-specific tissue autofluorescence is a persistent problem, as it creates a background which may obscure signals from weakly-labeled CTCs. Here we investigated the use of upconverting nanoparticles (UCNPs) as a contrast agent for DiFC, which in principle could significantly reduce the autofluorescence background and allow more sensitive detection of rare CTCs.Methods: We built a new UCNP-compatible DiFC instrument (U-DiFC), which uses a 980 nm laser and detects upconverted luminescence in the 520, 545 and 660 nm emission bands. We used NaYF4:Yb,Er UCNPs and several covalent and non-covalent surface modification strategies to improve their biocompatibility and cell uptake. We tested U-DiFC with multiple myeloma (MM) and Lewis lung carcinoma (LLC) cells in tissue-mimicking optical flow phantoms and in nude mice.Results: U-DiFC significantly reduced the background autofluorescence signals and motion artifacts from breathing in mice. Upconverted luminescence from NaYF4:Yb,Er microparticles (UμNP) and cells co-incubated with UCNPs were readily detectable with U-DiFC in phantoms, and from UCNPs in circulation in mice. However, we were unable to achieve reliable labeling of CTCs with UCNPs. Our data suggest that most (or all) of the measured U-DIFC signal in vitro and in vivo likely arose from unbound UCNPs or due to the uptake by non-CTC blood cells.Conclusion: UCNPs have a number of properties that make them attractive contrast agents for high-sensitivity detection of CTCs in the bloodstream with U-DiFC and other intravital imaging methods. More work is needed to achieve reliable and specific labeling of CTCs with UCNPs and verify long-term retention and viability of cells.Keywords: in vivo flow cytometry, upconverting nanoparticles, phosphorescenceBartosik PBFitzgerald JEEl Khatib MYaseen MAVinogradov SANiedre MDove Medical Pressarticlein vivo flow cytometryupconverting nanoparticlesphosphorescenceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 1709-1719 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	in vivo flow cytometry upconverting nanoparticles phosphorescence Medicine (General) R5-920
spellingShingle	in vivo flow cytometry upconverting nanoparticles phosphorescence Medicine (General) R5-920 Bartosik PB Fitzgerald JE El Khatib M Yaseen MA Vinogradov SA Niedre M Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
description	Peter B Bartosik,1 Jessica E Fitzgerald,1 Mirna El Khatib,2 Mohammad A Yaseen,3 Sergei A Vinogradov,2 Mark Niedre1 1Department of Bioengineering, Northeastern University, Boston, MA, USA; 2Department of Biochemistry and Biophysics, Perelman School of Medicine and Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; 3Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USACorrespondence: Mark Niedre Email m.niedre@neu.eduPurpose: We recently developed a new fluorescence-based technique called “diffuse in vivo flow cytometry” (DiFC) for enumerating rare circulating tumor cells (CTCs) directly in the bloodstream. Non-specific tissue autofluorescence is a persistent problem, as it creates a background which may obscure signals from weakly-labeled CTCs. Here we investigated the use of upconverting nanoparticles (UCNPs) as a contrast agent for DiFC, which in principle could significantly reduce the autofluorescence background and allow more sensitive detection of rare CTCs.Methods: We built a new UCNP-compatible DiFC instrument (U-DiFC), which uses a 980 nm laser and detects upconverted luminescence in the 520, 545 and 660 nm emission bands. We used NaYF4:Yb,Er UCNPs and several covalent and non-covalent surface modification strategies to improve their biocompatibility and cell uptake. We tested U-DiFC with multiple myeloma (MM) and Lewis lung carcinoma (LLC) cells in tissue-mimicking optical flow phantoms and in nude mice.Results: U-DiFC significantly reduced the background autofluorescence signals and motion artifacts from breathing in mice. Upconverted luminescence from NaYF4:Yb,Er microparticles (UμNP) and cells co-incubated with UCNPs were readily detectable with U-DiFC in phantoms, and from UCNPs in circulation in mice. However, we were unable to achieve reliable labeling of CTCs with UCNPs. Our data suggest that most (or all) of the measured U-DIFC signal in vitro and in vivo likely arose from unbound UCNPs or due to the uptake by non-CTC blood cells.Conclusion: UCNPs have a number of properties that make them attractive contrast agents for high-sensitivity detection of CTCs in the bloodstream with U-DiFC and other intravital imaging methods. More work is needed to achieve reliable and specific labeling of CTCs with UCNPs and verify long-term retention and viability of cells.Keywords: in vivo flow cytometry, upconverting nanoparticles, phosphorescence
format	article
author	Bartosik PB Fitzgerald JE El Khatib M Yaseen MA Vinogradov SA Niedre M
author_facet	Bartosik PB Fitzgerald JE El Khatib M Yaseen MA Vinogradov SA Niedre M
author_sort	Bartosik PB
title	Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
title_short	Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
title_full	Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
title_fullStr	Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
title_full_unstemmed	Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo
title_sort	prospects for the use of upconverting nanoparticles as a contrast agent for enumeration of circulating cells in vivo
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/267d304675964fc78ddf5446e45f6639
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Prospects for the Use of Upconverting Nanoparticles as a Contrast Agent for Enumeration of Circulating Cells in vivo

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