Metabolomic and Cellular Mechanistic Investigation of 10-Hydroxy-2-Decenoic-Acid-Functionalized Carbon Dots: Targeting Staphylococcus aureus and Host Inflammatory Microenvironment
Year: 2026
Type: article
Abstract: Chronic S. aureus infections couple microbial persistence with sustained host inflammation and oxidative stress, while conventional antibiotics face rising resistance and collateral immune disruption. We previously developed 10-HDA@CDs, conjugating this royal-jelly fatty acid onto a biocompatible nanocarrier to overcome its hydrophobicity and poor bioavailability, and reported the platform’s synthesis, characterization, and enhanced antibacterial activity. The present study extends this work by profiling cellular modulation of the host inflammatory and redox microenvironment and resolving the intracellular metabolic response of S. aureus. In heat-inactivated S. aureus-stimulated RAW 264.7 macrophages, 10-HDA@CDs at 20 μg/mL reduced NO by up to 91.7% and lowered ROS to 29.0% of stimulated levels, upregulated HO-1, and downregulated iNOS, MCP-1, and TNF-α, outperforming free 10-HDA. In TNF-α-impaired L929 fibroblasts, 10-HDA@CDs at 200 μg/mL restored viability to 73.4% (about 1.9-fold over free 10-HDA), downregulated IL-6, and upregulated IL-10, HO-1, and VEGF. Metabolomics identified 87 altered metabolites; decreased UDP-MurNAc, MurNAc-6P, and AnhMurNAc indicate perturbation of cell-wall precursor metabolism and amino-acid disturbance. These associations do not prove direct enzyme inhibition or a specific target; secondary injury effects cannot be excluded, and biocompatibility is confined to in vitro models. By simultaneously regulating host cytokine and redox responses and perturbing bacterial core metabolism, this food-derived, antibiotic-free nanoplatform advances a natural-product strategy against infection-associated inflammation.
DOI: 10.3390/jfb17110570
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7225637350