Nuclear localization of HIV-1 tat functionalized gold nanoparticles (Retracted Article)
Nuclear localization of HIV-1 tat functionalized gold nanoparticles (Retracted Article)
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DOI：
10.1109/tnb.2007.908973
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发表时间：
2007-12-01
影响因子：
3.9
通讯作者：
Curtis, A. S. G.
中科院分区：
文献类型：
--
作者：
Berry, C. C.;de la Fuente, J. M.;Curtis, A. S. G.
细胞膜的非渗透性限制了许多大分子的治疗用途，因此人们越来越努力地通过设计靶向细胞内递送的策略来绕过这一问题。在过去的十年中，一些细胞穿透肽，如HIV-1Tat肽，被证明可以穿过细胞膜，在那里完整的蛋白转导结构域(PTD)负责它们的细胞摄取，并在保持生物活性的同时到达细胞核。自那以后，人们发现PTDS可以实现共轭生物分子甚至纳米颗粒的细胞递送，但核递送仍然存在问题。本研究致力于用HIV-1 TAT PTD功能化不同大小的水溶性、生物相容的金纳米粒子，以生产核靶向剂。随后，这些颗粒在体外与人成纤维细胞系进行了测试，结果表明纳米颗粒成功地通过质膜转移，5 nm颗粒实现了核进入，而更大的30 nm颗粒保留在细胞质中，这表明通过核孔尺寸阻止了进入。
The impermeable nature of the cell plasma membrane limits the therapeutic uses of many macromolecules and there is therefore a growing effort to circumvent this problem by designing strategies for targeted intracellular delivery. During the last decade several cell penetrating peptides, such as the HIV-1 tat peptide, have been shown to traverse the cell membrane, where integral protein transduction domains (PTDs) are responsible for their cellular uptake, and to reach the nucleus while retaining biological activity. It has since been discovered that PTDs can enable the cellular delivery of conjugated biomolecules and even nanoparticles, but nuclear delivery has remained problematic. This present study focuses on the development of water soluble, biocompatible gold nanoparticles of differing size functionalized with the HIV-1 tat PTD with the aim of producing nuclear targeting agents. The particles were subsequently tested in vitro with a human fibroblast cell line, with results demonstrating successful nanoparticle transfer across the plasma membrane, with 5 nm particles achieving nuclear entry while larger 30 ran particles are retained in the cytoplasm, suggesting entry is blocked via nuclear pores dimensions.