Issue 23, 2022

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

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.

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

Supplementary files

Article information

Article type
Communication
Submitted
21 3 2022
Accepted
28 7 2022
First published
27 9 2022

Biomater. Sci., 2022,10, 6688-6697

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

J. L. Mangal, S. Inamdar, A. P. Suresh, M. M. C. S. Jaggarapu, A. Esrafili, N. D. Ng and A. P. Acharya, Biomater. Sci., 2022, 10, 6688 DOI: 10.1039/D2BM00415A

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