A combination dual-sized microparticle system modulates dendritic cells and prevents type 1 diabetes in prediabetic NOD mice

Clin Immunol. 2015 Sep;160(1):90-102. doi: 10.1016/j.clim.2015.03.023. Epub 2015 Apr 2.


We developed a novel poly(lactic-co-glycolic acid)-based, microparticle (MP) system providing concurrent delivery of multiple encapsulated immuno-suppressive factors and antigen, for in vivo conditioning of dendritic cells (DCs) toward a tolerance promoting pathway. Subcutaneous administration prevents onset of type 1 diabetes (T1D) in NOD mice. Two MP sizes were made: phagocytosable MPs were fabricated encapsulating vitamin D3 or insulin B(9-23) peptide, while unphagocytosable MPs were fabricated encapsulating TGF-β1 or GM-CSF. The combination of Vit D3/TGF-β1 MPs confers an immature and LPS activation-resistant phenotype to DCs, and MP-delivered antigen is efficiently and functionally presented. Notably, two subcutaneous injections into 4week old NOD mice using the combination of MPs encapsulating Vit D3, Ins B, TGF-β1 and GM-CSF protected 40% of mice from T1D development, significant in comparison to the control. This work represents one of the first applications of a biomaterial-based, MP vaccine system to successfully prevent autoimmune diabetes.

Keywords: Dendritic cells; Diabetes; Microparticle; NOD; Prevention; Tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cholecalciferol / pharmacology
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Drug Carriers*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immune Tolerance / immunology
  • Insulin / pharmacology
  • Lactic Acid*
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Particle Size
  • Peptide Fragments / pharmacology
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Transforming Growth Factor beta1 / pharmacology
  • Vaccines / administration & dosage*
  • Vaccines / immunology


  • Drug Carriers
  • Insulin
  • Lipopolysaccharides
  • Peptide Fragments
  • Transforming Growth Factor beta1
  • Vaccines
  • insulin B (9-23)
  • Cholecalciferol
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Granulocyte-Macrophage Colony-Stimulating Factor