Using gold nanoparticles for the enhanced delivery of auto-antigenic peptide in the NOD mouse model of autoimmune diabetes

Background

Gold nanoparticles (GNP) are used as a means of delivering drugs as well as proteins and peptides, particularly for cancer therapy. However, comparatively little is known regarding the use of gold nanoparticles for autoimmune disease therapy. The aim of our study was to test the effects of GNP conjugated to auto-antigenic peptide in the non obese diabetic (NOD) mouse model of Type 1 diabetes.

Methods

We covalently conjugated ultra-small 1-2nm gold nanoparticles to peptides that stimulate BDC2.5 TCR transgenic CD4 T cells, which recognise a hybrid chromogranin A-insulin peptide. BDC2.5 CD4 T cells were tested in vitro for induction of proliferation and cytokine production by peptide-GNP compared to unconjugated peptide alone. We also tested the safety and pharmacokinetics of intradermal injection of peptide-GNP into the skin of NOD mice.

Results

In vitro, we showed that peptide-GNP induced diabetogenic BDC2.5 CD4 T cells to express a more regulatory phenotype compared to peptide alone. indicated by increased TGFb and IL10 and decreased proliferation. Moreover in vivo, distribution of the peptide-GNP, following local delivery into the skin of NOD mice, was different to that seen when peptide was delivered alone. We observed increased antigen presentation to adoptively transferred BDC2.5 CD4 T cells in both the skin-draining and distal lymph nodes. Peptide alone however, was only presented in the skin-draining lymph node. Furthermore, GNPs were noted to remain at the site of injection, up to 8 weeks after delivery, both visually and by histological silver staining. However, no adverse effects or inflammation were seen.

Conclusion

Our results have demonstrated that auto-antigenic peptides bound to gold nanoparticles can be successfully and safely delivered using an intradermal route, enhancing distribution and pharmacokinetics as well as peptide presentation. Further experiments will be used to determine the effects of GNPs remaining in the skin.