Metabolic Reprogramming of Macrophages Exposed to Silk, Poly(lactic-co-glycolic acid), and Silica Nanoparticles

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. H-1 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 H-1 NMR metabolomics.

keywords

NMR-BASED METABONOMICS; DRUG-DELIVERY; IN-VITRO; BIOMEDICAL APPLICATIONS; CARBON NANOTUBES; BREAST-CANCER; ITACONIC ACID; ACTIVATION; GENERATION; EXPRESSION

subject category

Engineering; Science & Technology - Other Topics; Materials Science

authors

Saborano, R; Wongpinyochit, T; Totten, JD; Johnston, BF; Seib, FP; Duarte, IF

Groups

G5 - Biomimetic, Biological and Living Materials

Projects

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2013)

Rede Nacional de Ressonância Magnética Nuclear (PTNMR)

acknowledgements

This research was supported by a Research and Development Grant (No. 1715) from the University of Strathclyde (F.P.S. and I.F.D.) and by Marie Curie FP7 Career Integration Grant (No. 334134) (NanoTrac) within the seventh European funding programme (F.P.S.). J.D.T.' s Ph.D. studentship was supported through the EPSRC Doctoral Training Partnership (EP/M508159/1), University of Strathclyde. T.W.' s Ph.D. studentship was supported through a Collaborative International Research Programme: University of Strathclyde and Nanyang Technological University, Singapore. The authors would like to acknowledge that this work was carriered out in part at the CMAC National Facility, supported by a UK Research Partnership Fund award from the Higher Education Funding Council for England (Grant HH13054). The work was also developed in the scope of the project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), financed by national funds through the FCT/MEC and when appropriate cofinanced by FEDER under the PT2020 Partnership Agreement. The authors also acknowledge the Portuguese National NMR (PTNMR) Network, supported with FCT funds, Dr. Manfred Spraul, Bruker BioSpin (Germany), for providing access to NMR software and database, and Dr. Joana Carrola for technical support. I.F.D further acknowledges FCT/MCTES for a research contract under the Program "Investigador FCT" 2014.