PEGylation-dependent metabolic rewiring of macrophages with silk fibroin nanoparticles

John D. Totten, Thidarat Wongpinyochit, Joana Carrola, Iola F. Duarte, F. Philipp Seib

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
28 Downloads (Pure)


Silk fibroin nanoparticles are emerging as promising nanomedicines, but their full therapeutic potential is yet to be realized. These nanoparticles can be readily PEGylated to improve colloidal stability and to tune degradation and drug release profiles; however, the relationship between silk fibroin nanoparticle PEGylation and macrophage activation still requires elucidation. Here, we used in vitro assays and nuclear magnetic resonance based metabolomics to examine the inflammatory phenotype and metabolic profiles of macrophages following their exposure to unmodified or PEGylated silk fibroin nanoparticles. The macrophages internalized both types of nanoparticles, but they showed different phenotypic and metabolic responses to each nanoparticle type. Unmodified silk fibroin nanoparticles induced the upregulation of several processes, including production of proinflammatory mediators (e.g., cytokines), release of nitric oxide, and promotion of antioxidant activity. These responses were accompanied by changes in the macrophage metabolomic profiles that were consistent with a proinflammatory state and that indicated an increase in glycolysis and reprogramming of the tricarboxylic acid cycle and the creatine kinase/phosphocreatine pathway. By contrast, PEGylated silk fibroin nanoparticles induced milder changes to both inflammatory and metabolic profiles, suggesting that immunomodulation of macrophages with silk fibroin nanoparticles is PEGylation-dependent. Overall, PEGylation of silk fibroin nanoparticles reduced the inflammatory and metabolic responses initiated by macrophages, and this observation could be used to guide the therapeutic applications of these nanoparticles.

Original languageEnglish
Pages (from-to)14515-14525
Number of pages11
JournalACS Applied Materials and Interfaces
Issue number16
Early online date12 Apr 2019
Publication statusPublished - 24 Apr 2019


  • silk
  • fibroin
  • silk nanoparticles
  • NMR metabolomics
  • macrophages


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