Zarebkohan Amir, Najafi Farhood, Moghimi Hamid Reza, Hemmati Mohammad, Deevband Mohammad Reza, Kazemi Bahram
Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
Iran J Pharm Res. 2016 Fall;15(4):629-640.
Glioma, as a primary tumor of central nervous system, is the main cause of death in patients with brain cancer. Therefore, development of an efficient strategy for treatment of glioma is worthy. The aim of the current study was to develop a SRL peptide-coated dendrimer as a novel dual gene delivery system for targeting the LRP receptor, an up-regulated gene in both BBB and glioma cells. To perform this investigation, our newly developed nanocarrier (PAMAM-PEG-SRL) was used for gene delivery to C6 glioma cell lines. DNA (GFP) was loaded in these functionalized nanoparticles and their cellular uptake/distribution and gene transfection efficacy was evaluated by fluorescence and confocal microscopy. In vitro studies showed that SRL-modified nanoparticles have good transfection efficacy. Results revealed improved gene transfection efficiency of newly-synthesized delivery system. We also found that lactoferrin, as a LRP ligand, reduced the gene transfection efficacy of the delivery system due to its higher affinity compared to SRL peptides (Competitive inhibition). The present results suggest that the synthesized delivery system has the potential to be used as an alternative targeted drug delivery system for brain tumors.
神经胶质瘤作为中枢神经系统的原发性肿瘤，是脑癌患者死亡的主要原因。因此，开发一种有效的神经胶质瘤治疗策略很有价值。本研究的目的是开发一种SRL肽包被的树枝状大分子，作为一种新型的双基因递送系统，用于靶向低密度脂蛋白受体相关蛋白（LRP），该基因在血脑屏障和神经胶质瘤细胞中均上调。为了进行这项研究，我们新开发的纳米载体（PAMAM-PEG-SRL）被用于向C6神经胶质瘤细胞系递送基因。将DNA（绿色荧光蛋白）负载到这些功能化纳米颗粒中，并通过荧光和共聚焦显微镜评估其细胞摄取/分布和基因转染效率。体外研究表明，SRL修饰的纳米颗粒具有良好的转染效率。结果显示新合成的递送系统的基因转染效率有所提高。我们还发现，乳铁蛋白作为一种LRP配体，由于其与SRL肽相比具有更高的亲和力，降低了递送系统的基因转染效率（竞争性抑制）。目前的结果表明，合成的递送系统有潜力用作脑肿瘤的替代靶向药物递送系统。
