Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.
Nanomedicine. 2011 Jun;7(3):315-23. doi: 10.1016/j.nano.2010.10.004. Epub 2010 Nov 2.
Efficacy of siRNAs as potential anticancer therapeutics can be increased by their targeted delivery into cancer cells via tumor-specific ligands. Phage display offers a unique approach to identify highly specific and selective ligands that can deliver nanocarriers to the site of disease. In this study, we proved a novel approach for intracellular delivery of siRNAs into breast cancer cells through their encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins. The targeted siRNA liposomes were obtained by a fusion of two parental liposomes containing spontaneously inserted siRNA and fusion phage proteins. The presence of pVIII coat protein fused to a MCF-7 cell-targeting peptide DMPGTVLP in the liposomes was confirmed by Western blotting. The novel phage-targeted siRNA-nanopharmaceuticals demonstrate significant down-regulation of PRDM14 gene expression and PRDM14 protein synthesis in the target MCF-7 cells. This approach offers the potential for development of new anticancer siRNA-based targeted nanomedicines.
In this study, the authors report a novel approach for targeted intracellular delivery of siRNAs into breast cancer cells through encapsulation into liposomes targeted to the tumor cells with preselected intact phage proteins.
通过肿瘤特异性配体将 siRNA 靶向递送至癌细胞中,可以提高其作为潜在抗癌治疗剂的疗效。噬菌体展示技术为识别能够将纳米载体递送至疾病部位的高度特异性和选择性配体提供了一种独特的方法。在这项研究中,我们通过将 siRNA 包裹在靶向肿瘤细胞的脂质体中,证明了一种通过预先选择的完整噬菌体蛋白将 siRNA 递送至乳腺癌细胞内的新方法。通过融合两个含有自发插入的 siRNA 和融合噬菌体蛋白的亲本脂质体来获得靶向 siRNA 的脂质体。通过 Western blot 证实了融合至 MCF-7 细胞靶向肽 DMPGTVLP 的 pVIII 衣壳蛋白存在于脂质体中。新型噬菌体靶向 siRNA-纳米药物在靶标 MCF-7 细胞中显著下调 PRDM14 基因表达和 PRDM14 蛋白合成。这种方法为开发新的基于 siRNA 的靶向抗癌纳米药物提供了潜力。
在这项研究中,作者报告了一种通过将 siRNA 包裹在靶向肿瘤细胞的脂质体中,通过预先选择的完整噬菌体蛋白将 siRNA 靶向递送至乳腺癌细胞内的新方法。