Taghavi Pourianazar Negar, Gunduz Ufuk
Middle East Technical University, Department of Biotechnology, 06800 Ankara, Turkey.
Middle East Technical University, Department of Biotechnology, 06800 Ankara, Turkey; Middle East Technical University, Department of Biological Sciences, 06800 Ankara, Turkey.
Biomed Pharmacother. 2016 Mar;78:81-91. doi: 10.1016/j.biopha.2016.01.002. Epub 2016 Jan 19.
One major application of nanotechnology in cancer treatment involves designing nanoparticles to deliver drugs, oligonucleotides, and genes to cancer cells. Nanoparticles should be engineered so that they could target and destroy tumor cells with minimal damage to healthy tissues. This research aims to develop an appropriate and efficient nanocarrier, having the ability of interacting with and delivering CpG-oligodeoxynucleotides (CpG-ODNs) to tumor cells. CpG-ODNs activate Toll-like receptor 9 (TLR9), which can generate a signal cascade for cell death. In our study, we utilized three-layer magnetic nanoparticles composed of a Fe3O4 magnetic core, an aminosilane (APTS) interlayer and a cationic poly(amidoamine) (PAMAM) dendrimer. This will be a novel targeted delivery system to enhance the accumulation of CpG-ODN molecules in tumor cells. The validation of CpG-ODN binding to DcMNPs was performed using agarose gel electrophoresis, UV-spectrophotometer, XPS analyses. Cytotoxicity of conjugates was assessed in MDA-MB231 and SKBR3 cancer cells based on cell viability by XTT assay and flow cytometric analysis. Our results indicated that the synthesized DcMNPs having high positive charges on their surface could attach to CpG-ODN molecules via electrostatic means. These nanoparticles with the average sizes of 40±10nm bind to CpG-ODN molecules efficiently and induce cell death in MDA-MB231 and SKBR3 tumor cells and could be considered a suitable targeted delivery system for CpG-ODN in biomedical applications. The magnetic core of these nanoparticles represents a promising option for selective drug targeting as they can be concentrated and held in position by means of an external magnetic field.
纳米技术在癌症治疗中的一个主要应用涉及设计纳米颗粒,以将药物、寡核苷酸和基因递送至癌细胞。纳米颗粒的设计应使其能够靶向并破坏肿瘤细胞,同时对健康组织的损害最小。本研究旨在开发一种合适且高效的纳米载体,使其具有与CpG-寡脱氧核苷酸(CpG-ODNs)相互作用并将其递送至肿瘤细胞的能力。CpG-ODNs可激活Toll样受体9(TLR9),进而引发细胞死亡的信号级联反应。在我们的研究中,我们使用了由Fe3O4磁芯、氨基硅烷(APTS)中间层和阳离子聚(酰胺胺)(PAMAM)树枝状大分子组成的三层磁性纳米颗粒。这将是一种新型的靶向递送系统,可增强CpG-ODN分子在肿瘤细胞中的积累。使用琼脂糖凝胶电泳、紫外分光光度计、XPS分析对CpG-ODN与双氰胺磁性纳米颗粒(DcMNPs)的结合进行了验证。基于XTT法和流式细胞术分析细胞活力,评估了共轭物在MDA-MB231和SKBR3癌细胞中的细胞毒性。我们的结果表明,表面带有高正电荷的合成DcMNPs可通过静电方式附着于CpG-ODN分子。这些平均尺寸为40±10nm的纳米颗粒能有效结合CpG-ODN分子,并在MDA-MB231和SKBR3肿瘤细胞中诱导细胞死亡,在生物医学应用中可被视为一种适合CpG-ODN的靶向递送系统。这些纳米颗粒的磁芯代表了选择性药物靶向的一个有前景的选择,因为它们可以通过外部磁场进行聚集并固定在特定位置。