Gold nanorods enhance different immune cells and allow for efficient targeting of CD4+ Foxp3+ Tregulatory cells

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.

Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy

“…Gold nanoparticles, such as 20 nm citrate-covered gold nanoparticles (cit-AuNP), have been demonstrated to have important antiinflammatory properties in the brain of sepsis and are promising as adjunctive agents in sepsis treatment with antibiotics to avoid SAE (111). Hyperforin-loaded gold nanoparticles, gold nanorods/compounds and anti-inflammatory nanoparticles have the ability to improve symptoms by inhibiting the differentiation of Th1 and Th17, while promoting the accumulation of T regs and Th2 in the treatment of EAE, cancer, and muscular dystrophy (112)(113)(114). Therefore, gold nanoparticles can have therapeutic interest to promote T regs accumulation in the context of SAE.…”

Investigating the Potential of Cuboidal Nanometals as Protein Subunit Vaccine Carriers In Vivo

“…It was demonstrated that when C57BL/6 splenocytes were treated with polyethylene‐glycol‐coated gold nanorods (PEG–AuNRs) and PEG–AuNRs covered with a thin layer of silver, only PEG–AuNRs could enhance cluster of differentiation (CD)4+ Foxp3+ regulatory T cells response. [ 13 ]…”

“…[11,12] Moreover, AuNPs of diverse size and shape have been shown to induce expression of distinct inflammatory cytokines in bone-marrowderived dendritic cells (BMDCs). [13,14] Different surface chemistries of AuNPs have also been shown to affect inflammatory processes, as measured by downregulated interleukin (IL)-1𝛽 levels, both in vivo and in vitro using a human monocyte cell line. [15] Furthermore, the surface composition of AuNPs affects activation and function of different dendritic cells (DCs) and T cell subsets.…”

“…It was demonstrated that when C57BL/6 splenocytes were treated with polyethylene-glycol-coated gold nanorods (PEG-AuNRs) and PEG-AuNRs covered with a thin layer of silver, only PEG-AuNRs could enhance cluster of differentiation (CD)4+ Foxp3+ regulatory T cells response. [13] AuNPs have been utilized in several vaccine models, including for dengue fever, Hepatitis E, and classical swine fever. [6,7,16] Consistent with in vitro immunogenicity data, in vaccine models, AuNP adjuvanticity has been linked to their physicochemical properties.…”