Zwitterionic Biocompatible Quantum Dots for Wide pH Stability and Weak Nonspecific Binding to Cells

Zwitterionic Biocompatible Quantum Dots for Wide pH Stability and Weak Nonspecific Binding to Cells
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DOI:
10.1021/nn900600w
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发表时间:
2009-09-01
期刊:
影响因子:
17.1
通讯作者:
Nienhaus, G. Ulrich
Nienhaus, G. Ulrich
中科院分区:
材料科学1区
文献类型:
--
作者:
Breus, Vladimir V.;Heyes, Colin D.;Nienhaus, G. Ulrich

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水溶性量子点(QD)在生命科学中的应用受到其在生理介质中胶体稳定性差以及与生物物质(特别是细胞膜)的非特异性相互作用的限制。我们研究了两性离子 D-青霉胺涂层 QD (DPA-QD) 和传统使用的羧化 11-巯基十一烷酸涂层 QD (MUA-QD) 的胶体稳定性和与活细胞的非特异性相互作用,并发现 DPA-QD 的明显优势。在单分子荧光实验中,DPA-QD 在生理相关 pH 范围 5-9 内没有表现出聚集,而 MUA-QD 在 pH 9 以下表现出显着聚集。在暴露于活的 Mono Mac 6 细胞后,具有整体电荷中性表面的 DPA-QD 表现出与细胞膜的弱相互作用,并且可以通过用缓冲液冲洗轻松去除。相比之下,高电荷的 MUA-QD 与细胞紧密结合,即使用缓冲溶液大量冲洗也无法去除。与之前报道的半胱氨酸涂层 QD 相比,DPA-QD 即使在强氧化条件下也表现出较高的化学稳定性。这种有益的特性可能是由于甲基对其 β-碳原子的空间效应而减少了 DPA 配体之间的相互作用。
Applications of water-soluble quantum dots (QDs) in the life sciences are limited by their poor colloidal stability in physiological media and nonspecific interaction with biomatter, particularly cell membranes. We have studied colloidal stability and nonspecific interactions with living cells for zwitterionic D-penicillamine-coated QDs (DPA-QDs) and the traditionally used carboxylated 11-mercaptoundecanoic acid-coated QDs (MUA-QDs) and found clear advantages of DPA-QDs. In single molecule fluorescence experiments, DPA-QDs showed no aggregation over the physiologically relevant pH range of 5-9, whereas MUA-QDs showed significant aggregation below pH 9. Upon exposure to living Mono Mac 6 cells, DPA-QDs, which possess overall charge-neutral surfaces, exhibited weak interactions with the cell membrane and were easily removed by flushing with buffer. By contrast, the highly charged MUA-QDs strongly associated with the cells and could not be removed even by extensive rinsing with buffer solution. DPA-QDs exhibit a high chemical stability even in strongly oxidizing conditions, in contrast to cysteine-coated QDs reported earlier. This beneficial property may arise from reduced interactions between DPA ligands due to steric effects of the methyl groups on their beta-carbon atoms.