Short term, low dose alpha-ketoglutarate based polymeric nanoparticles with methotrexate reverse rheumatoid arthritis symptoms in mice and modulate T helper cell responses

Joslyn L. Mangal, Sahil Inamdar, Abhirami P. Suresh, Madhan Mohan Chandra Sekhar Jaggarapu, Arezoo Esrafili, Nathan D. Ng, Abhinav P. Acharya

Research output: Contribution to journalArticlepeer-review

Abstract

Activated effector T cells induce pro-inflammatory responses in rheumatoid arthritis (RA) which then lead to inflammation of the joints. In this report, we demonstrate that polymeric nanoparticles with alpha keto-glutarate (aKG) in their polymer backbone (termed as paKG NPs) modulate T cell responses in vitro and in vivo. Impressively, a low dose of only three administrations of methotrexate, a clinically and chronically administered drug for RA, in conjunction with two doses of paKG NPs, reversed arthritis symptoms in collagen-induced arthritis (CIA) mice. This was further followed by significant decreases in pro-inflammatory antigen-specific T helper type 17 (TH17) responses and a significant increase in anti-inflammatory regulatory T cell (TREG) responses when CIA treated splenic cells were isolated and re-exposed to the CIA self-antigen. Overall, this study supports the concurrent and short term, low dose of paKG NPs and methotrexate for the reversal of RA symptoms.

Original languageEnglish (US)
Pages (from-to)6688-6697
Number of pages10
JournalBiomaterials Science
Volume10
Issue number23
DOIs
StatePublished - Sep 27 2022

ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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