Cytosolic delivery of membrane-penetrating QDs into T cell lymphocytes: implications in immunotherapy and drug delivery.
Cytosolic delivery of membrane-penetrating QDs into T cell lymphocytes: implications in immunotherapy and drug delivery.
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DOI：
10.1039/d0nr08362c
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发表时间：
2021-03-18
期刊：
影响因子：
6.7
通讯作者：
Hu YS
中科院分区：
文献类型：
--
作者：
Jing H;Pálmai M;Saed B;George A;Snee PT;Hu YS
我们报告了T细胞淋巴细胞中膜穿透半导体量子点（QD）的单粒子表征。我们功能化的水溶性CdSe/CdZnS量子点与细胞穿透肽组成的Asp-Ser-Ser（DSS）重复序列。DSS和无肽对照QD显示浓度依赖性内化。单粒子成像的强度分布揭示了DSS-QD在T细胞胞质溶胶中保持单体状态的倾向，而对照QD形成明显的簇。单粒子追踪表明，单个量子点团簇的迁移率与聚集状态呈正相关。对照QD的显著部分与T细胞内的内体标志物共定位，并且对于DSS-QD，百分比下降至9%。内吞抑制废除了控制量子点的内化，而DSS-QD内化仅轻度下降，这表明一种替代的细胞进入机制。使用3D单粒子跟踪，我们捕获了DSS-QD的快速穿膜活性。表征活T细胞中的膜穿透活性的能力为通过使用新型纳米材料优化基因治疗和药物递送创造了进展。将DSS-QD细胞内递送到T细胞淋巴细胞中的单粒子研究。
We report single-particle characterization of membrane-penetrating semiconductor quantum dots (QDs) in T cell lymphocytes. We functionalized water-soluble CdSe/CdZnS QDs with a cell-penetrating peptide composed of an Asp-Ser-Ser (DSS) repeat sequence. DSS and peptide-free control QDs displayed concentration-dependent internalization. Intensity profiles from single-particle imaging revealed a propensity of DSS-QDs to maintain a monomeric state in the T cell cytosol, whereas control QDs formed pronounced clusters. Single-particle tracking showed a positive correlation between individual QD clusters’ mobility and aggregation state. A significant portion of control QDs colocalized with the endosome marker inside the T cells, and the percentage dropped to 9% for DSS-QDs. Endocytosis inhibition abrogated the internalization of control QDs, while DSS-QD internalization only mildly decreased, suggesting an alternative cell-entry mechanism. Using 3D single-particle tracking, we captured the rapid membrane-penetrating activity of a DSS-QD. The ability to characterize membrane penetrating activities in live T cells creates inroads for the optimization of gene therapy and drug delivery through the use of novel nanomaterials. Single-particle studies of intracellular delivery of DSS-QDs into T cell lymphocytes.
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