Molecular Dendritic Transporter Nanoparticle Vectors Provide Efficient Intracellular Delivery of Peptides
Molecular Dendritic Transporter Nanoparticle Vectors Provide Efficient Intracellular Delivery of Peptides
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DOI：
10.1021/nn800679z
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发表时间：
2009-02-01
期刊：
影响因子：
17.1
通讯作者：
Harth, Eva
中科院分区：
文献类型：
--
作者：
Hamilton, Sharon K.;Harth, Eva
我们提出了一个模块化的传递系统，它是由两个主要的大分子构建块，树突状分子转运分子和聚合物支架的尺寸尺寸为5 - 10 nm的合成。缀合的树突状分子转运蛋白单元被证明对于将聚合物纳米颗粒递送到3 T3细胞中是关键的，并且说明了树突状分子转运蛋白促进源自分子内链塌陷过程的聚合物颗粒的细胞内摄取。在一系列修饰步骤中，引入吡啶基二硫代接头以与含有半胱氨酸氨基加成单元的肽序列进行硫醇-二硫键交换反应，以提供具有可裂解的二硫键接头的肽-纳米颗粒缀合物。纳米颗粒缀合物的细胞内摄取和肽货物的递送通过用Alexa Fluor 568染料和哺乳动物细胞系如NIH 3 T3细胞中肽上的荧光素（FITC）标记物双标记纳米颗粒来研究。在这项工作中，我们已经证明了一种新的纳米级递送系统的组装，其中缀合的树突状分子转运分子促进了具有多达25个拷贝的肽货物的纳米颗粒-肽缀合物的快速细胞摄取，以建立用于实施蛋白质和寡核苷酸药物的新场所。
We present the synthesis of a modular delivery system that is composed of two main macromolecular building blocks, dendritic molecular transporter molecules and a polymeric scaffold in a size dimension of 5 - 10 nm. The conjugated dendritic molecular transporter units proved to be critical for the delivery of the polymer nanoparticle into 3T3 cells and illustrates the dendritic molecular transporter promoted intracellular uptake of polymer particles derived from intramolecular chain collapse processes. In a sequence of modification steps, pyridinyldithio linker was introduced to undergo thiol-disulfide exchange reactions with peptide sequences containing cysteine amino add units to furnish peptide-nanoparticle conjugates with cleavable disulfide linkers. The intracellular uptake of the nanoparticle conjugates and the delivery of the peptidic cargo were studied via dual labeling of the nanoparticle with Alexa Fluor 568 dye and fluorescein (FITC) markers on the peptide in mammalian cell lines such as NIH 3T3 cells via confocal microscopy. In this work, we have demonstrated the assembly of a novel nanoscopic delivery system in which the conjugated dendritic molecular transporter molecules facilitated the rapid cellular uptake of a nanoparticle-peptide conjugate with up to 25 copies of peptidic cargo to establish new venues for the implementation of protein and oligonucleotide drugs.