Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia; Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia.
Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia.
J Control Release. 2021 Sep 10;337:629-644. doi: 10.1016/j.jconrel.2021.08.010. Epub 2021 Aug 8.
Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.
核因子-κB（NF-κB）是一种独特的蛋白质复合物，在肺部炎症和呼吸功能障碍中起着重要作用。NF-κB 信号通路因此成为开发潜在药理干预的途径，特别是在慢性炎症经常持续活跃并在疾病的发病机制和进展中起关键作用的情况下。NF-κB 诱饵寡脱氧核苷酸（ODN）是双链的，并携带 NF-κB 结合序列。它们可以阻止 NF-κB 介导的炎症细胞因子的形成，因此已被用于治疗各种慢性炎症性疾病。然而，由于其较差的药代动力学特性、不稳定性、细胞酶降解以及细胞摄取率低，裸诱饵 ODN 的全身给药限制了其治疗效果。结构修饰和纳米技术在增强有效治疗物质的药代动力学特性方面显示出了有希望的结果，并且在治疗哮喘、慢性阻塞性肺疾病和囊性纤维化等呼吸系统疾病方面也显示出了巨大的潜力。在这篇综述中，我们研究了 NF-κB 激活在呼吸系统疾病中的作用以及诱饵 ODN 治疗应用的最新进展。此外，我们还强调了使用诱饵 ODN 作为治疗分子的局限性和挑战、诱饵 ODN 的细胞摄取以及当前对新型递药系统的需求，以提供高效的诱饵 ODN 递药。此外，这篇综述为讨论诱饵 ODN 的存在提供了一个共同的平台，并概述了针对呼吸疾病中 NF-κB 靶向的最新一代包裹诱饵 ODN 的递药系统的观点。
