Recent trends of NFkB decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases

• Published in: Journal of controlled release 2021-09, Vol.337, p.629
• Main Authors: Mehta, Meenu, Paudel, Keshav Raj, Shukla, Shakti Dhar, Allam, Venkata, Kannaujiya, Vinod Kumar, Panth, Nisha, Das, Amlan, Parihar, Vipan Kumar, Chakraborty, Amlan, Ali, Md Khadem, Jha, Niraj Kumar, Xenaki, Dikaia, Su, Qian Peter, Wich, Peter Richard, Adams, Jon, Hansbro, Philip Michael, Chellappan, Dinesh Kumar, Oliver, Brian Gregory George, Dua, Kamal
• Format: Article
• Language: English
• Subjects: Decoy oligodeoxynucleotide; Novel delivery systems; Nuclear factor kappa B; Respiratory disorder
• ISSN: 1873-4995; 0168-3659
• DOI: 10.1016/j.jconrel.2021.08.010

Nuclear factor Kappa B (NFicB) is a unique protein complex that plays a major role in lung inflammation and respi-ratory dysfunction. The NFicB 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. NFicB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFicB binding sequences. They prevent the formation of NFicB-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 NFicB activation in respiratory diseases and recent advancements in the thera-peutic 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 NFxB in respiratory diseases.