2. Academic Validation
  3. Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism

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

  • J Mater Chem B. 2020 Jun 24;8(24):5195-5203. doi: 10.1039/d0tb00790k.
Joslyn L Mangal 1,  Sahil Inamdar 2,  Yi Yang 2,  Subhadeep Dutta 3,  Mamta Wankhede 2,  Xiaojian Shi 4,  Haiwei Gu 4,  Matthew Green 2,  Kaushal Rege 5,  Marion Curtis 6,  Abhinav P Acharya 7
Affiliations

Affiliations

  • 1 Biological Design Graduate Program, School for Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA. abhi.acharya@asu.edu.
  • 2 Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85281, USA.
  • 3 School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA.
  • 4 College of Health Solutions, Arizona State University, Phoenix, AZ 85281, USA.
  • 5 Biological Design Graduate Program, School for Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA. abhi.acharya@asu.edu and Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85281, USA and School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USA.
  • 6 Mayo Clinic, Department of Immunology, Scottsdale, AZ 85259, USA.
  • 7 Biological Design Graduate Program, School for Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA. abhi.acharya@asu.edu and Chemical Engineering, School for the Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ 85281, USA.
PMID: 32427266 DOI: 10.1039/d0tb00790k
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.

Figures
Products