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基于 NaYF 的上转换纳米粒子,具有优化的膦酸酯涂层,可提高人内皮细胞的化学稳定性和活力。

NaYF-based upconverting nanoparticles with optimized phosphonate coatings for chemical stability and viability of human endothelial cells.

机构信息

Jožef Stefan Institute, Department for Materials Synthesis, Jamova 39, 1000 Ljubljana, Slovenia.

University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.

出版信息

Methods Appl Fluoresc. 2021 Dec 22;10(1). doi: 10.1088/2050-6120/ac41ba.

Abstract

The increasing interest in upconverting nanoparticles (UCNPs) in biodiagnostics and therapy fuels the development of biocompatible UCNPs platforms. UCNPs are typically nanocrystallites of rare-earth fluorides codoped with Yband Eror Tm. The most studied UCNPs are based on NaYFbut are not chemically stable in water. They dissolve significantly in the presence of phosphates. To prevent any adverse effects on the UCNPs induced by cellular phosphates, the surfaces of UCNPs must be made chemically inert and stable by suitable coatings. We studied the effect of various phosphonate coatings on chemical stability andcytotoxicity of the Yb,Er-codoped NaYFUCNPs in human endothelial cells obtained from cellular line Ea.hy926. Cell viability of endothelial cells was determined using the resazurin-based assay after the short-term (15 min), and long-term (24 h and 48 h) incubations with UCNPs dispersed in cell-culture medium. The coatings were obtained from tertaphosphonic acid (EDTMP), sodium alendronate and poly(ethylene glycol)-neridronate. Regardless of the coating conditions, 1 - 2 nm-thick amorphous surface layers were observed on the UCNPs with transmission electron microscopy. The upconversion fluorescence was measured in the dispersions of all UCNPs. Surafce quenching in aqueous suspensions of the UCNPs was reduced by the coatings. The dissolution degree of the UCNPs was determined from the concentration of dissolved fluoride measured with ion-selective electrode after the ageing of UCNPs in water, physiological buffer (i.e., phosphate-buffered saline-PBS) and cell-culture medium. The phosphonate coatings prepared at 80 °C significantly suppressed the dissolution of UCNPs in PBS while only minor dissolution of bare and coated UCNPs was measured in water and cell-culture medium. The viability of human endothelial cells was significantly reduced when incubated with UCNPs, but it increased with the improved chemical stability of UCNPs by the phosphonate coatings with negligible cytotoxicity when coated with EDTMP at 80 °C.

摘要

上转换纳米粒子(UCNPs)在生物诊断和治疗中的应用日益受到关注,这推动了生物相容性 UCNPs 平台的发展。UCNPs 通常是掺有 Y 带和 Eror Tm 的稀土氟化物纳米晶。研究最多的 UCNPs 基于 NaYF,但在水中化学稳定性不高。它们在存在磷酸盐的情况下会显著溶解。为了防止细胞磷酸盐对 UCNPs 产生任何不利影响,必须通过合适的涂层使 UCNPs 的表面具有化学惰性和稳定性。我们研究了各种膦酸酯涂层对 Yb,Er 共掺杂 NaYF UCNPs 在人内皮细胞中的化学稳定性和细胞毒性的影响,内皮细胞取自细胞系 Ea.hy926。用基于 Resazurin 的测定法在短时间(15 分钟)和长时间(24 小时和 48 小时)与分散在细胞培养基中的 UCNPs 孵育后,测定内皮细胞的活力。涂层是由三膦酸(EDTMP)、阿仑膦酸钠和聚乙二醇-奈立膦酸制备的。无论涂层条件如何,在透射电子显微镜下观察到 UCNPs 上都有 1-2nm 厚的非晶表面层。在所有 UCNPs 的分散体中测量了上转换荧光。涂层减少了 UCNPs 在水悬浮液中的表面猝灭。通过在水中、生理缓冲液(即磷酸盐缓冲盐水-PBS)和细胞培养基中老化 UCNPs 后用离子选择性电极测量溶解的氟化物浓度来确定 UCNPs 的溶解程度。在 80°C 下制备的膦酸酯涂层显著抑制了 PBS 中 UCNPs 的溶解,而在水和细胞培养基中仅测量到裸和涂覆 UCNPs 的轻微溶解。当与 UCNPs 孵育时,人内皮细胞的活力显著降低,但当用 80°C 下的 EDTMP 涂覆时,UCNPs 的化学稳定性得到改善,细胞毒性可忽略不计,细胞活力增加。

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