Germanane Quantum Dots Promote Metabolic Reprogramming of Immune Cells Toward Regulatory T Cells and Suppress Inflammation In Vitro and In Vivo.

Recently, nanomaterials have emerged as a tool in developing novel therapies against inflammatory diseases. Metabolic changes in immune cells direct the phenotype and function of the host immune system. Therefore, next-generation immunomodulatory biomaterials should be designed to target metabolic pathways and trigger specific changes in immune cells to direct their fate toward an anti-inflammatory phenotype. The current study reports the fabrication and first application of germanane quantum dots (GeHQDs) to modulate inflammation in cell culture and in vivo mouse model. Using rational design and synthesis strategies, our GeHQDs leverage the intrinsic anti-inflammatory properties of germanane to provide a novel nanoplatform to trigger metabolic reprogramming of immune cells toward an anti-inflammatory phenotype. These GeHQDs are spontaneously uptaken into the immune cells and trigger a switch in their phenotype toward regulatory T (Treg) cells. Metabolomic analysis suggested a downregulation in glycolytic flux and upregulation in fatty acid oxidation with an increase in mitochondrial respiration in the GeHQDs-treated group, which is a typical signature of Treg cells. In an in vivo mouse model of systemic inflammation, GeHQDs treatment upregulated the circulating Treg cell number, improved the metabolomic profile and downregulated inflammation. The current study presents a new paradigm in targeting inflammatory diseases by modulating immune cell metabolism using next-generation nanomaterials.