Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

Joslyn L. Mangal, Sahil Inamdar, Yi Yang, Subhadeep Dutta, Mamta Wankhede, Xiaojian Shi, Haiwei Gu, Matthew Green, Kaushal Rege, Marion Curtis, Abhinav P. Acharya

Research output: Contribution to journalArticle

Abstract

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro. These metabolic changes resulted in modulation of MHC-II, CD86 expression in DCs, and altered the frequency of regulatory T cells (Tregs), and T-helper type-1/2/17 cells in vitro. This unique strategy of intracellular delivery of key-metabolites in a sustained manner provides a new direction in immunometabolism field-based immunotherapy with potential applications in different diseases associated with immune disorders.

Original languageEnglish (US)
Pages (from-to)5195-5203
Number of pages9
JournalJournal of Materials Chemistry B
Volume8
Issue number24
DOIs
StatePublished - Jun 28 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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  • Cite this

    Mangal, J. L., Inamdar, S., Yang, Y., Dutta, S., Wankhede, M., Shi, X., Gu, H., Green, M., Rege, K., Curtis, M., & Acharya, A. P. (2020). Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism. Journal of Materials Chemistry B, 8(24), 5195-5203. https://doi.org/10.1039/d0tb00790k