Farahmand Leila, Darvishi Behrad, Majidzadeh-A Keivan
a Recombinant Proteins Department , Motamed Breast Cancer Research Center, ACECR , Tehran , Iran.
b Genetics Department , Motamed Breast Cancer Research Center, ACECR , Tehran , Iran.
Drug Deliv. 2017 Nov;24(1):1249-1261. doi: 10.1080/10717544.2017.1370511.
As a prototypical pro-inflammatory transcription factor, constitutive activation of NF-κB signaling pathway has been reported in several chronic inflammatory disorders including inflammatory bowel disease, cystic fibrosis, rheumatoid arthritis and cancer. Application of decoy oligodeoxynucleotides (ODNs) against NF-κB, as an effective molecular therapy approach, has brought about several promising outcomes in treatment of chronic inflammatory disorders. However, systematic administration of these genetic constructs is mostly hampered due to their instability, rapid degradation by nucleases and poor cellular uptake. Both chemical modification and application of delivery systems have shown to effectively overcome some of these limitations. Among different administered delivery systems, nanomaterials have gained much attention for delivering NF-κB decoy ODNs owing to their high loading capacity, targeted delivery and ease of synthesis. In this review, we highlight some of the most recently developed nanomaterial-based delivery systems for overcoming limitations associated with clinical application of these genetic constructs.
作为一种典型的促炎转录因子，在包括炎症性肠病、囊性纤维化、类风湿性关节炎和癌症在内的几种慢性炎症性疾病中，均已报道了NF-κB信号通路的组成性激活。应用针对NF-κB的诱饵寡脱氧核苷酸（ODN）作为一种有效的分子治疗方法，已在慢性炎症性疾病的治疗中取得了一些有前景的成果。然而，由于这些基因构建体的不稳定性、易被核酸酶快速降解以及细胞摄取不良，其系统性给药大多受到阻碍。化学修饰和递送系统的应用均已证明能有效克服其中一些局限性。在不同的给药递送系统中，纳米材料因其高负载能力、靶向递送和易于合成，在递送NF-κB诱饵ODN方面备受关注。在本综述中，我们重点介绍了一些最近开发的基于纳米材料的递送系统，以克服与这些基因构建体临床应用相关的局限性。
