Mechanisms of Quantum Dot Nanoparticle Cellular Uptake
Mechanisms of Quantum Dot Nanoparticle Cellular Uptake
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DOI：
10.1093/toxsci/kfp087
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发表时间：
2009-07-01
影响因子：
3.8
通讯作者：
Monteiro-Riviere, Nancy A.
中科院分区：
文献类型：
--
作者：
Zhang, Leshuai W.;Monteiro-Riviere, Nancy A.
由于量子点具有上级的光致发光和光稳定性，量子点在生物学和医学领域有着广泛的应用。然而，QD摄取的毒性和机制知之甚少。具有655 nm的发射波长的QD纳米颗粒是椭圆形的，并且由具有硫化锌壳的镉/硒化物核组成。我们已经表明，与羧酸表面涂层的QD被人表皮角质形成细胞（HEK）中的脂筏识别，但不被网格蛋白或小窝。QD被内化到早期内体中，然后转移到晚期内体或溶酶体中。此外，使用24种内吞干扰剂来研究QD进入细胞的机制。我们的研究结果表明，QD内吞途径主要由G蛋白偶联受体相关途径和低密度脂蛋白受体/清道夫受体调节，而其他内吞干扰剂可能发挥作用，但抑制作用较小。最后，通过活/死细胞测定，在HEK中使用20 nM剂量在48 h显示QD的低毒性，但在24 h未显示。QD诱导更多的肌动蛋白丝在细胞质中形成，这与镉引起的肌动蛋白解聚不同。这些发现提供了对QD纳米颗粒在细胞中摄取的具体机制的深入了解。QD纳米颗粒的表面涂层、尺寸和电荷是确定哺乳动物细胞中纳米颗粒摄取如何发生以用于癌症诊断和治疗以及药物递送的重要参数。
Due to the superior photoemission and photostability characteristics, quantum dots (QD) are novel tools in biological and medical applications. However, the toxicity and mechanism of QD uptake are poorly understood. QD nanoparticles with an emission wavelength of 655 nm are ellipsoid in shape and consist of a cadmium/selenide core with a zinc sulfide shell. We have shown that QD with a carboxylic acid surface coating were recognized by lipid rafts but not by clathrin or caveolae in human epidermal keratinocytes (HEKs). QD were internalized into early endosomes and then transferred to late endosomes or lysosomes. In addition, 24 endocytic interfering agents were used to investigate the mechanism by which QD enter cells. Our results showed that QD endocytic pathways are primarily regulated by the G-protein-coupled receptor associated pathway and low density lipoprotein receptor/scavenger receptor, whereas other endocytic interfering agents may play a role but with less of an inhibitory effect. Lastly, low toxicity of QD was shown with the 20nM dose in HEK at 48 h but not at 24 h by the live/dead cell assay. QD induced more actin filaments formation in the cytoplasm, which is different from the actin depolymerization by cadmium. These findings provide insight into the specific mechanism of QD nanoparticle uptake in cells. The surface coating, size, and charge of QD nanoparticles are important parameters in determining how nanoparticle uptake occurs in mammalian cells for cancer diagnosis and treatment, and drug delivery.