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

Meenu Mehta, Keshav Raj Paudel, Shakti Dhar Shukla, Venkata Sita Rama Raju Allam, Vinod Kumar Kannaujiya, Nisha Panth, Amlan Das, Vipan Kumar Parihar, Amlan Chakraborty, Md Khadem Ali, Niraj Kumar Jha, Dikaia Xenaki, Qian Peter Su, Peter Richard Wich, Jon Adams, Philip Michael Hansbro, Dinesh Kumar Chellappan, Brian Gregory George Oliver, Kamal Dua

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)629-644
Number of pages16
JournalJournal of Controlled Release
Volume337
DOIs
Publication statusPublished - 10 Sep 2021

Keywords

  • Decoy oligodeoxynucleotide
  • Novel delivery systems
  • Nuclear factor kappa B
  • Respiratory disorder

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