Abstract
Monitoring macrophage metabolism in response to nanoparticle exposure provides new insights into biological outcomes, such as inflammation or toxicity, and supports the design of tailored nanomedicines. This paper describes the metabolic signature of macrophages exposed to nanoparticles ranging in diameter from 100 to 125 nm and made from silk, poly(lactic-co-glycolic acid) or silica. Nanoparticles of this size and type are currently at various stages of preclinical and clinical development for drug delivery applications. 1 H NMR analysis of cell extracts and culture media is used to quantify the changes in the intracellular and extracellular metabolomes of macrophages in response to nanoparticle exposure. Increased glycolytic activity, an altered tricarboxylic acid cycle, and reduced ATP generation are consistent with a proinflammatory phenotype. Furthermore, amino acids possibly arising from autophagy, the creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature is a common response to all nanoparticles tested; however, the direction and magnitude of some variations are clearly nanoparticle specific, indicating material-induced biological specificity. Overall, metabolic reprogramming of macrophages can be achieved with nanoparticle treatments, modulated through the choice of the material, and monitored using 1 H NMR metabolomics.
Highlights
Amino acids possibly arising from autophagy, the seasonal influenza, diabetes, smoking creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles
Cells exposed to poly(lactic-co-glycolic acid) (PLGA) nanoparticles showed no signs of cell coating, instead showing loose packing around the cells (Figure 1b)
We assessed the metabolomic response of macrophages toward silk, PLGA, and silica nanoparticles that are in preclinical
Summary
Amino acids possibly arising from autophagy, the seasonal influenza, diabetes, smoking creatine kinase/phosphocreatine system, and a few osmolytes and antioxidants emerge as important players in the metabolic reprogramming of macrophages exposed to nanoparticles. This metabolic signature is a common response to all nanoparticles tested; the direction and magnitude of some variations are clearly nanoparticle specific, indicating material-induced cessation, and cancer.[2] Nanoparticles designed for the treatment of solid tumors are typically in the 100 nm size range and exploit the leaky vasculature and reduced lymphatic drainage of tumors to achieve passive targeting,[3] a phenomenon known biological specificity.
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