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Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping

BACKGROUND: Suitable fluorophores are the core of fluorescence imaging. Among the most exciting, yet controversial, labels are quantum dots (QDs) with their unique optical and chemical properties, but also considerable toxicity. This hinders QDs applicability in living systems. Surface chemistry has...

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Autores principales: Buchtelova, Hana, Strmiska, Vladislav, Skubalova, Zuzana, Dostalova, Simona, Michalek, Petr, Krizkova, Sona, Hynek, David, Kalina, Lukas, Richtera, Lukas, Moulick, Amitava, Adam, Vojtech, Heger, Zbynek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907456/
https://www.ncbi.nlm.nih.gov/pubmed/29673366
http://dx.doi.org/10.1186/s12951-018-0369-7
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author Buchtelova, Hana
Strmiska, Vladislav
Skubalova, Zuzana
Dostalova, Simona
Michalek, Petr
Krizkova, Sona
Hynek, David
Kalina, Lukas
Richtera, Lukas
Moulick, Amitava
Adam, Vojtech
Heger, Zbynek
author_facet Buchtelova, Hana
Strmiska, Vladislav
Skubalova, Zuzana
Dostalova, Simona
Michalek, Petr
Krizkova, Sona
Hynek, David
Kalina, Lukas
Richtera, Lukas
Moulick, Amitava
Adam, Vojtech
Heger, Zbynek
author_sort Buchtelova, Hana
collection PubMed
description BACKGROUND: Suitable fluorophores are the core of fluorescence imaging. Among the most exciting, yet controversial, labels are quantum dots (QDs) with their unique optical and chemical properties, but also considerable toxicity. This hinders QDs applicability in living systems. Surface chemistry has a profound impact on biological behavior of QDs. This study describes a two-step synthesis of QDs formed by CdTe core doped with Schiff base ligand for lanthanides [Ln (Yb(3+), Tb(3+) and Gd(3+))] as novel cytocompatible fluorophores. RESULTS: Microwave-assisted synthesis resulted in water-soluble nanocrystals with high colloidal and fluorescence stability with quantum yields of 40.9–58.0%. Despite induction of endocytosis and cytoplasm accumulation of Yb- and TbQDs, surface doping resulted in significant enhancement in cytocompatibility when compared to the un-doped CdTe QDs. Furthermore, only negligible antimigratory properties without triggering formation of reactive oxygen species were found, particularly for TbQDs. Ln-doped QDs did not cause observable hemolysis, adsorbed only a low degree of plasma proteins onto their surface and did not possess significant genotoxicity. To validate the applicability of Ln-doped QDs for in vitro visualization of receptor status of living cells, we performed a site-directed conjugation of antibodies towards immuno-labeling of clinically relevant target—human norepinephrine transporter (hNET), over-expressed in neuroendocrine tumors like neuroblastoma. Immuno-performance of modified TbQDs was successfully tested in distinct types of cells varying in hNET expression and also in neuroblastoma cells with hNET expression up-regulated by vorinostat. CONCLUSION: For the first time we show that Ln-doping of CdTe QDs can significantly alleviate their cytotoxic effects. The obtained results imply great potential of Ln-doped QDs as cytocompatible and stable fluorophores for various bio-labeling applications.
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spelling pubmed-59074562018-04-30 Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping Buchtelova, Hana Strmiska, Vladislav Skubalova, Zuzana Dostalova, Simona Michalek, Petr Krizkova, Sona Hynek, David Kalina, Lukas Richtera, Lukas Moulick, Amitava Adam, Vojtech Heger, Zbynek J Nanobiotechnology Research BACKGROUND: Suitable fluorophores are the core of fluorescence imaging. Among the most exciting, yet controversial, labels are quantum dots (QDs) with their unique optical and chemical properties, but also considerable toxicity. This hinders QDs applicability in living systems. Surface chemistry has a profound impact on biological behavior of QDs. This study describes a two-step synthesis of QDs formed by CdTe core doped with Schiff base ligand for lanthanides [Ln (Yb(3+), Tb(3+) and Gd(3+))] as novel cytocompatible fluorophores. RESULTS: Microwave-assisted synthesis resulted in water-soluble nanocrystals with high colloidal and fluorescence stability with quantum yields of 40.9–58.0%. Despite induction of endocytosis and cytoplasm accumulation of Yb- and TbQDs, surface doping resulted in significant enhancement in cytocompatibility when compared to the un-doped CdTe QDs. Furthermore, only negligible antimigratory properties without triggering formation of reactive oxygen species were found, particularly for TbQDs. Ln-doped QDs did not cause observable hemolysis, adsorbed only a low degree of plasma proteins onto their surface and did not possess significant genotoxicity. To validate the applicability of Ln-doped QDs for in vitro visualization of receptor status of living cells, we performed a site-directed conjugation of antibodies towards immuno-labeling of clinically relevant target—human norepinephrine transporter (hNET), over-expressed in neuroendocrine tumors like neuroblastoma. Immuno-performance of modified TbQDs was successfully tested in distinct types of cells varying in hNET expression and also in neuroblastoma cells with hNET expression up-regulated by vorinostat. CONCLUSION: For the first time we show that Ln-doping of CdTe QDs can significantly alleviate their cytotoxic effects. The obtained results imply great potential of Ln-doped QDs as cytocompatible and stable fluorophores for various bio-labeling applications. BioMed Central 2018-04-19 /pmc/articles/PMC5907456/ /pubmed/29673366 http://dx.doi.org/10.1186/s12951-018-0369-7 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Buchtelova, Hana
Strmiska, Vladislav
Skubalova, Zuzana
Dostalova, Simona
Michalek, Petr
Krizkova, Sona
Hynek, David
Kalina, Lukas
Richtera, Lukas
Moulick, Amitava
Adam, Vojtech
Heger, Zbynek
Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title_full Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title_fullStr Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title_full_unstemmed Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title_short Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping
title_sort improving cytocompatibility of cdte quantum dots by schiff-base-coordinated lanthanides surface doping
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907456/
https://www.ncbi.nlm.nih.gov/pubmed/29673366
http://dx.doi.org/10.1186/s12951-018-0369-7
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