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通过席夫碱配位镧系元素表面掺杂来提高 CdTe 量子点的细胞相容性。

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

机构信息

Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, 613 00, Brno, Czech Republic.

Central European Institute of Technology, Brno University of Technology, Purkynova 123, 612 00, Brno, Czech Republic.

出版信息

J Nanobiotechnology. 2018 Apr 19;16(1):43. doi: 10.1186/s12951-018-0369-7.

Abstract

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, Tb and Gd)] 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.

摘要

背景

合适的荧光团是荧光成像的核心。在最令人兴奋但也最有争议的标签中,量子点 (QD) 具有独特的光学和化学性质,但也有相当大的毒性。这阻碍了 QD 在活系统中的应用。表面化学对 QD 的生物行为有深远的影响。本研究描述了一种两步合成法,由 CdTe 核掺杂希夫碱基配体形成的量子点用于镧系元素 [Ln (Yb、Tb 和 Gd)] 作为新型细胞相容的荧光团。

结果

微波辅助合成得到了水溶性纳米晶体,具有高胶体和荧光稳定性,量子产率为 40.9-58.0%。尽管 Yb 和 TbQD 诱导了内吞作用和细胞质积累,但与未掺杂的 CdTe QD 相比,表面掺杂显著提高了细胞相容性。此外,仅发现了微不足道的抗迁移特性,而没有引发活性氧的形成,特别是对于 TbQD。Ln 掺杂的 QD 不会引起可观察到的溶血,仅在其表面吸附少量的血浆蛋白,并且不具有显著的遗传毒性。为了验证 Ln 掺杂的 QD 适用于体外可视化活细胞受体状态,我们进行了抗体的定向偶联,用于免疫标记临床相关的靶标-人去甲肾上腺素转运体(hNET),hNET 在神经内分泌肿瘤如神经母细胞瘤中过度表达。修饰后的 TbQD 的免疫性能在 hNET 表达不同的不同类型细胞中以及在 hNET 表达通过 vorinostat 上调的神经母细胞瘤细胞中进行了成功测试。

结论

我们首次表明,Ln 掺杂可以显著减轻 CdTe QD 的细胞毒性。所得结果表明,Ln 掺杂的 QD 作为细胞相容和稳定的荧光团具有很大的潜力,可用于各种生物标记应用。

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