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Further progress in cytosolic cellular delivery of quantum dots

机译:量子点的胞质细胞递送的进一步进展

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Currently there is considerable interest in using bioconjugated nanoparticles for in vivo imaging, biosensing and theranostics. Luminescent CdSe/ZnS core shell semiconductor quantum dots (QDs) have unique optical properties and bioconjugation capabilities that make them ideal prototypes for these purposes. We have previously described the metal-affinity association between the imidazole groups of terminal hexahistidine residues of peptides and proteins and the ZnS shell of quantum dots as a useful bioconjugation technique. We have also demonstrated that QDs labeled with an oligohistidine-tagged cell penetrating peptide (CPP) derived from the HIV TAT-protein could undergo specific endocytosis-mediated cellular uptake in both HEK293T/17 and COS-1 cells. However, the QDs were predominantly sequestered in the endosomes. This remains a significant hindrance to future potential cellular imaging applications which require the QDs to access other subcellular organelles. Here we describe the testing of several cytosolic QD delivery modalities including microinjection, the commercial cytosolic delivery agent PULSin, and the cytosolic delivery peptide Palm-1. Palm-1, a palmitylated peptide that is capable of both cellular uptake and rapid endosomal escape in multiple cell lines without concomitant toxicity~([3]), is shown to be the superior method for cytosolic delivery of QDs. Potential intracellular applications for this peptide are discussed.
机译:当前,对于将生物共轭的纳米颗粒用于体内成像,生物传感和治疗诊断学有相当大的兴趣。发光的CdSe / ZnS核壳半导体量子点(QD)具有独特的光学特性和生物共轭能力,使其成为用于这些目的的理想原型。先前我们已经描述了肽和蛋白质的末端六组氨酸残基的咪唑基团与量子点的ZnS壳之间的金属亲和力关联作为一种有用的生物共轭技术。我们还证明,用衍生自HIV TAT蛋白的寡组氨酸标记的细胞穿透肽(CPP)标记的QD可以在HEK293T / 17和COS-1细胞中经历特定的内吞介导的细胞摄取。但是,量子点主要被隔离在内体中。这仍然是未来潜在的细胞成像应用的重大障碍,因为后者需要量子点访问其他亚细胞器。在这里,我们描述了几种细胞质QD传递方式的测试,包括显微注射,商业的细胞质传递剂PULSin和细胞质传递肽Palm-1。 Palm-1是一种棕榈酸酯化的肽,能够在多种细胞系中吸收细胞并快速逃逸内体,而没有伴随的毒性[[3]],已被证明是QD胞质递送的上乘方法。讨论了该肽在细胞内的潜在应用。

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