Targeting tuberculosis infection in macrophages using chitosan oligosaccharide nanoplexes

Abstract

Targeting bacterial infections using RNA interference (RNAi) has been a relatively nascent area of research as compared with cancer and viral infections. Exploring this area is especially vital due to the prevalence of numerous challenging bacterial infections that have been persistent despite treatment with antibiotics or antibiotic-loaded delivery systems. In this investigation, we formulate siRNA nanoparticle complexes, using cationic water-soluble chitosan polymer, for intracellular delivery into macrophages that serve as reservoirs of numerous pathogenic bacteria, including Mycobacterium tuberculosis (Mtb). Cationic chitosan oligosaccharide nanoparticles of size 215.3 ± 4.19 nm were formulated by ionotropic gelation and were effectively delivered along with siRNA into the macrophages, without any obvious cytotoxicity. The siRNA-loaded nanoparticles resulted in more than two-fold down-regulation of the host gene, Bfl1/A1, as compared with untreated controls. Since the over expression of host gene Bfl1/A1 favours for survival of Mtb within macrophages, the nanoparticles present a promising potential for developing anti-tuberculosis therapy.

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Funding

Mr. Uday Koli was financially supported by the Department of Biotechnology (BT/PR5372/MED/29/489/2012), Govt. of India and the Department of Atomic Energy (DAE: 2012/20/37B/08/BRNS) for fellowship. Dr. Prajakta Dandekar was financially supported by the Ramanujan Fellowship Grant (SR/S2/RJN-139/2011), DST, Govt. of India. Dr. Ratnesh Jain was financially supported by the Ramalingaswami Fellowship (BT/RLF/RE-ENTRY/51/2011), DBT, Govt. of India.

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Koli, U., Nilgiriwala, K., Sriraman, K. et al. Targeting tuberculosis infection in macrophages using chitosan oligosaccharide nanoplexes. J Nanopart Res 21, 200 (2019). https://doi.org/10.1007/s11051-019-4623-1

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Keywords

  • Mycobacteria
  • Bfl-1/a1
  • siRNA delivery
  • Chitosan oligosaccharides
  • Macrophages
  • Nanomedicine