ABSTRACT
Gold nanoparticles (AuNPs) hold great promise in nanomedicine, yet their successful clinical translation has not been realized. Some challenges include effective AuNP targeting and delivery to improve modulation of immune cells of interest while limiting potential adverse effects. In order to overcome these challenges, we must fully understand how AuNPs impact different immune cell subsets, particularly within the dendritic cell and T cell compartments. Herein, we show that polyethylene glycol coated (PEG) gold nanorods (AuNRs) and PEG AuNRs covered with a thin layer of silver (AuNR/Ag) may enhance the immune response towards immune suppression or activation. We also studied the ability to enhance CD4+ Foxp3+ Tregs in vitro using AuNRs functionalized with interleukin 2 (IL2), a cytokine that is important in Treg development and homeostasis. Our results indicate that AuNRs enhance different immune cells and that NP composition matters in immune targeting. This knowledge will help us understand how to better design AuNRs to target and enhance the immune system.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , Forkhead Transcription Factors/metabolism , Gold/pharmacology , Metal Nanoparticles/administration & dosage , Nanotubes/chemistry , Animals , CD4-Positive T-Lymphocytes/metabolism , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Immune System/drug effects , Immune System/metabolism , Immunity/drug effects , Interleukin-2/metabolism , Mice , Mice, Inbred C57BL , Polyethylene Glycols/chemistry , Silver/administration & dosageABSTRACT
The use of synthetic materials for biomedical applications is ever expanding. One of the major requirements for these materials is biocompatibility, which includes prevention of immune system responses. Due to the inherent complexity of their structural composition, the polyurethane (PU) family of polymers is being used in a variety of medical applications, from soft and hard tissue scaffolds to intricate coatings on implantable devices. Herein, we investigated whether two polymer materials, D3 and D7, induced an immune response, measured by their effects on a dendritic cell (DC) line, JAWS II. Using a lactate dehydrogenase cytotoxicity assay and Annexin V/PI staining, we found that the PU materials did not induce cytotoxicity in DC cells. Using confocal microscopy, we also showed that the materials did not induce activation or maturation, as compared to positive controls. This was confirmed by looking at various markers, CD80, CD86, MHC class I, and MHC class II, via flow cytometry. Overall, the results indicated that the investigated PU films are biocompatible in terms of immunotoxicology and immunogenicity and show great promise for use in regenerative medicine.
