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

Mehta M 1 , Paudel KR 2 , Shukla SD 3 , Allam VSRR 4 , Kannaujiya VK 5 , Panth N 6 Show all authors , Das A 7 , Parihar VK 8 , Chakraborty A 9 , Ali MK 10 , Jha NK 11 , Xenaki D 12 , Su QP 13 , Wich PR 14 , Adams J 15 , Hansbro PM 2 , Chellappan DK 16 , Oliver BGG 17 , Dua K 18

Affiliations 

  • 1 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
  • 2 Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia
  • 3 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia
  • 4 Department of Medical Biochemistry and Microbiology, Uppsala University, 75237, Sweden
  • 5 School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia
  • 6 Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia
  • 7 National Institute of Biomedical Genomics, Kalyani, Nadia 741235, WB, India
  • 8 Department of Radiation Oncology, NASA Specialized Center of Research, University of California, Irvine 92697, USA
  • 9 Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia
  • 10 Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA; Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford University, Stanford, CA, USA
  • 11 Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, Uttar Pradesh, 201310, India
  • 12 Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
  • 13 School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW 2007, Australia
  • 14 School of Chemical Engineering, University of New South Wales, Sydney, NSW 2052, Australia; Australian Centre for NanoMedicine and Centre for Advanced Macromolecular Design, University of New South Wales, Sydney, NSW 2052, Australia
  • 15 Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia
  • 16 Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
  • 17 School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia; Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia. Electronic address: Brian.Oliver@uts.edu.au
  • 18 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. Electronic address: Kamal.Dua@uts.edu.au
J Control Release, 2021 09 10;337:629-644.
PMID: 34375688 DOI: 10.1016/j.jconrel.2021.08.010

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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