Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic‐co‐glycolic acid), and Silica Nanoparticles. Issue 14 (8th May 2017)

• Record Type: Journal Article
• Authors: Saborano, Raquel; Wongpinyochit, Thidarat; Totten, John D.; Johnston, Blair F.; Seib, F. Philipp; Duarte, Iola F.
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 14(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-05-08
• Subjects: macrophages -- NMR metabolomics -- PLGA nanoparticles -- silica nanoparticles -- silk nanoparticles; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201601240
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : The changes in macrophage metabolism upon exposure to silk, poly(lactic‐ co ‐glycolic acid), or silica nanoparticles are revealed through NMR metabolomics. Main findings comprise increased glycolysis, altered tricarboxylic acid cycle, reduced ATP generation, activation of the creatine/phosphocreatine system, and changes in osmolytes and antioxidants. Metabolic reprogramming of macrophages can be achieved with nanoparticle treatments and monitored using NMR metabolomics.