Abstract
BackgroundSuitable 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 (Yb3+, Tb3+ and Gd3+)] as novel cytocompatible fluorophores.ResultsMicrowave-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.ConclusionFor 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.
Highlights
Suitable fluorophores are the core of fluorescence imaging
We focused on evaluation of viability, endocytosis, antimigratory properties, induction of formation of reactive oxygen species (ROS) and stimulatory/ inhibitory effect of Ln-doped quantum dots (QDs) on the expression of proteins involved in fundamental biological processes, including apoptosis, cell cycle, signaling or metal homeostasis
We focused on immuno-labeling of clinically relevant target—human norepinephrine transporter, which is overexpressed in neuroendocrine tumors like neuroblastoma, and which is targeted by one of the most widely used theranostic agent metaiodobenzylguanidine [21]
Summary
Among the most exciting, yet controversial, labels are quantum dots (QDs) with their unique optical and chemical properties, and considerable toxicity. This hinders QDs applicability in living systems. Quantum dots (QDs) are semiconductor nanocrystals (~ 2 to 10 nm) with unique optical and electrical properties [1]. Due to these properties, QDs have undisputable potential to revolutionize biological imaging and to Buchtelova et al J Nanobiotechnol (2018) 16:43. To achieve cyto- and biocompatibility, attention has been concentrated towards carbon-based QDs [13], or surface modifications of metal-based QDs [14]
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