Cell-type specific and cytoplasmic targeting of PEGylated carbon nanotube-based nanoassemblies
Cell-type specific and cytoplasmic targeting of PEGylated carbon nanotube-based nanoassemblies
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DOI：
10.1166/jnn.2008.501
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发表时间：
2008-05-01
影响因子：
--
通讯作者：
Bottini, Massimo
中科院分区：
文献类型：
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作者：
Cato, Matthew H.;D'Annibale, Federica;Bottini, Massimo
在本文中，我们报告了一个多价，细胞类型特异性和细胞质输送系统的基础上单壁碳纳米管的制造。后者通过吸附由荧光染料偶联的中性抗生物素蛋白功能化的生物素化PEG链终止的磷脂进行功能化，随后用用于T细胞受体后信号转导内吞作用的抗体（抗CD 3 β和抗CD 28）和用于破坏溶酶体隔室的合成融合聚合物进行功能化。仿生纳米组装体由聚乙二醇化的单个/非常小的碳纳米管束组成，其平均长度和标准偏差分别为176 nm和77 nm。纳米组装体在生理条件下稳定分散，通过常规光学和共聚焦显微镜可见，并且特异性靶向体外和活体动物中的T细胞。向纳米组装体中添加融合聚合物不影响细胞摄取，并且允许在体外和动物中释放到靶细胞的胞质溶胶中。目前的手稿是第一份关于碳纳米管在完整动物的特定细胞类型中的细胞质递送的报告，并为它们作为体内细胞内递送系统的使用铺平了道路。
In this paper we report the fabrication of a multivalent, cell-type specific and cytoplasmic delivery system based on single-walled carbon nanotubes. The latter were functionalized through adsorption of phospholipids terminated by biotinylated PEG chains functionalized with fluorochrome-coupled neutravidin, and subsequently with antibodies (anti-CD3 epsilon and anti-CD28) for T cell receptor post-signaling endocytosis and a synthetic fusogenic polymer for disruption of lysosomal compartments. The biomimetic nanoassemblies were composed by PEGylated individual/very small bundles of carbon nanotubes having an average length and a standard deviation of 176 nm and 77 nm, respectively. The nanoassemblies were stably dispersed under physiological conditions, visible by conventional optical and confocal microscopy and specifically targeted to T cells both in vitro and in living animals. The addition of a fusogenic polymer to the nanoassemblies did not affect the cellular uptake and allowed the release into the cytosol of the targeted cells both in vitro and in the animals. The present manuscript is the first report about the cytoplasmic delivery of carbon nanotubes in a specific cell type in intact animals and paves the way for their use as in vivo intracellular delivery systems.