PEGylation-Dependent Metabolic Rewiring of Macrophages with Silk Fibroin Nanoparticles

authors	Totten, JD; Wongpinyochit, T; Carrola, J; Duarte, IF; Seib, FP
nationality	International
journal	ACS APPLIED MATERIALS & INTERFACES
author keywords	silk; fibroin; silk nanoparticles; NMR metabolomics; macrophages
keywords	TUMOR-ASSOCIATED MACROPHAGES; NITRIC-OXIDE; ACTIVATED MACROPHAGES; IN-VITRO; HEMOCOMPATIBILITY; BIOCOMPATIBILITY; COLOCALIZATION; PRINCIPLES; SUCCINATE; DESIGN
abstract	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.
publisher	AMER CHEMICAL SOC
issn	1944-8244
isbn	1944-8252
year published	2019
volume	11
issue	16
beginning page	14515
ending page	14525
digital object identifier (doi)	10.1021/acsami.8b18716
web of science category	Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
subject category	Science & Technology - Other Topics; Materials Science
unique article identifier	WOS:000466052800003