Multifunctional gold nanoparticle-peptide complexes for nuclear targeting
Multifunctional gold nanoparticle-peptide complexes for nuclear targeting
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DOI：
10.1021/ja0296935
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发表时间：
2003-04-23
影响因子：
15
通讯作者：
Feldheim, DL
中科院分区：
文献类型：
--
作者：
Tkachenko, AG;Xie, H;Feldheim, DL
探讨了多肽修饰的金纳米颗粒靶向HepG2细胞的能力。研究了5种多肽/纳米颗粒复合体，它们分别修饰了(1)来自SV-40病毒的核定位信号(NLS)；(2)腺病毒NLS；(3)腺病毒受体介导的内吞作用(RME)多肽；(4)一个含腺病毒RME和NLS的长肽；(5)作为独立片段附着在纳米颗粒上的腺病毒RME和NLS多肽。使用金纳米粒子是因为它们很容易使用视频增强的色差干涉对比显微镜进行识别，并且它们是构建多功能核靶向载体的优秀支架。例如，仅用NLS多肽修饰的颗粒不能从质膜外靶向HepG2细胞的细胞核，因为它们要么不能进入细胞，要么被困在内吞体内。NLS/RME颗粒(4)和(5)的组合确实到达了细胞核；然而，当这两个信号作为单独的短片段连接到纳米颗粒上时，核靶向性比一个长肽更有效。这些研究突出了与核靶向相关的挑战，以及设计多功能纳米结构材料作为细胞内诊断和治疗输送工具的潜在优势。
The ability of peptide-modified gold nanoparticles to target the nucleus of HepG2 cells was explored. Five peptide/nanoparticle complexes were investigated, particles modified with (1) the nuclear localization signal (NLS) from the SV 40 virus; (2) the adenovirus NLS; (3) the adenovirus receptor-mediated endocytosis (RME) peptide; (4) one long peptide containing the adenovirus RME and NLS; and (5) the adenovirus RME and NLS peptides attached to the nanoparticle as separate pieces. Gold nanoparticles were used because they are easy to identify using video-enhanced color differential interference contrast microscopy, and they are excellent scaffolds from which to build multifunctional nuclear targeting vectors. For example, particles modified solely with NLS peptides were not able to target the nucleus of HepG2 cells from outside the plasma membrane, because they either could not enter the cell or were trapped in endosomes. The combination of NLS/RME particles (4) and (5) did reach the nucleus; however, nuclear targeting was more efficient when the two signals were attached to nanoparticles as separate short pieces versus one long peptide. These studies highlight the challenges associated with nuclear targeting and the potential advantages of designing multifunctional nanostructured materials as tools for intracellular diagnostics and therapeutic delivery.