Surface-Ligand-Dependent Cellular Interaction, Subcellular Localization, and Cytotoxicity of Polymer-Coated Quantum Dots
Surface-Ligand-Dependent Cellular Interaction, Subcellular Localization, and Cytotoxicity of Polymer-Coated Quantum Dots
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DOI：
10.1021/cm902989f
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发表时间：
2010-04-13
影响因子：
8.6
通讯作者：
Ying, Jackie Y.
中科院分区：
文献类型：
--
作者：
Tan, Shawn J.;Jana, Nikhil R.;Ying, Jackie Y.
纳米粒子和量子点（QD）为基础的生物探针正在成为替代小分子探针在体外和体内的应用。然而，它们的细胞相互作用和细胞摄取机制与小分子探针显著不同，并且对表面配体极其敏感。这些在纳米颗粒和量子点作为细胞探针的发展中存在障碍。本工作的重点是合成各种功能化的量子点与可调的表面电荷，疏水性，功能化与聚乙二醇（PEG化）和它们的细胞相互作用。我们发现，纳米尺寸的探针的表面官能团显着决定了它们的细胞相互作用，亚细胞定位，和细胞毒性。对于所有类型的量子点，观察到剂量依赖性的相互作用，但阳离子表面电荷或疏水性将增加与阴离子表面电荷相比的细胞相互作用。阳离子量子点迅速进入细胞并诱导细胞毒性，但疏水量子点粘附在细胞膜上，并没有进入细胞。阳离子量子点的PEG化降低了它们的非特异性结合和细胞毒性，并且需要更高浓度的量子点才能进入细胞。在这些结果的基础上，我们能够设计具有平衡的疏水性和表面电荷的不同功能化QD纳米探针用于细胞膜标记和亚细胞靶向。机制研究表明网格蛋白介导的相互作用和吸收的所有类型的量子点。20-50 nm颗粒的细胞相互作用和摄取主要由其表面电荷和穿透细胞膜的能力决定，并且纳米颗粒在细胞中的最终目的地可以通过表面配体的适当设计来控制。
Nanoparticle- and quantum-dot (QD)-based bioprobes are emerging as alternatives to small-molecule probes for in vitro and in vivo applications. However, their cellular interaction and cell uptake mechanism are significantly different from those of small-molecule probes and are extremely sensitive to surface ligands. These present a barrier in the development of nanoparticles and QDs as cellular probes. This work focused on the synthesis of various functionalized QDs with tunable surface charge, hydrophobicity, and functionalization with poly(ethylene glycol) (PEGylation) and their cellular interaction. We found that the surface functional groups of nanometer-sized probes significantly dictated their cellular interaction, subcellular localization, and cytotoxicity. A dose-dependent interaction was observed for all types of QDs, but the cationic surface charge or hydrophobicity would increase the cellular interaction as compared to the anionic surface charge. Cationic QDs rapidly entered cells and induced cytotoxicity, but hydrophobic QDs were stuck to the cell membrane and did not enter the cells. PEGylation of cationic QDs reduced their nonspecific binding and cytotoxicity, and a higher concentration of QDs was required for cellular entry. On the basis of these results, we were able to design different functionalized QD nanoprobes with balanced hydrophobicity and surface charge for cell membrane labeling and subcellular targeting. Mechanistic studies indicated a clathrin-mediated interaction and uptake for all types of QDs. The cellular interaction and uptake of 20-50 nm particles were primarily determined by their surface charges and ability to penetrate the cellular membrane, and the final destinations of the nanoparticles in the cell could be controlled by the appropriate design of surface ligands.