Plant-derived extracellular vesicles deliver spermidine to reprogram macrophage metabolism and ameliorate rheumatoid arthritis.
7 affiliations
- 1Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
- 2Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.
- 3Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, 518036, China.
- 4Department of Rheumatology & Immunology, Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Peking University People's Hospital, Beijing, 100044, China.
- 5Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518036, China. [email protected].
- 6Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China. [email protected].
- 7Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, 518036, China. [email protected].
Abstract
Rheumatoid arthritis (RA) is driven by macrophage-mediated synovial inflammation closely linked to metabolic dysfunction, highlighting immunometabolism as a therapeutic target. Here, we engineered spermidine-loaded red cabbage-derived extracellular vesicles (RCEVs@SPD) as a plant-based nanoplatform to reprogram macrophage bioenergetics. In LPS-stimulated macrophages, RCEVs@SPD suppressed pro-inflammatory polarization and enhanced mitochondrial function, as evidenced by increased ATP production and mitochondrial membrane potential. Assay-based measurements further showed reduced extracellular acidification rate (ECAR) and elevated oxygen consumption rate (OCR), indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS). Untargeted LC-MS metabolomics revealed coordinated alterations in pathways supporting mitochondrial cofactor biosynthesis, redox balance, and central carbon metabolism. Transcriptomic analysis confirmed enrichment of OXPHOS and mitochondrial respiration gene signatures with concomitant repression of glycolytic programs and PI3K-AKT signaling. In vivo, RCEVs@SPD significantly alleviated collagen-induced arthritis, improved joint histopathology, and promoted anti‑inflammatory macrophage polarization. Notably, systemic macrophage depletion abolished the additional therapeutic benefit of RCEVs@SPD, demonstrating macrophage dependence. Collectively, these findings establish plant-derived extracellular vesicles as a biocompatible delivery system that potentiates spermidine to restore macrophage metabolic balance and mitigate RA pathology.
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BibTeX
@article{wang2026plantderived,
title = {{Plant-derived extracellular vesicles deliver spermidine to reprogram macrophage metabolism and ameliorate rheumatoid arthritis.}},
author = {Xiaocheng Wang and Jiaxin He and Yixiang Hong and Xingyue Zeng and Min Li and Shixiong Cao and Renge Liang and Gengmin Zhou and Qingwen Wang},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04836-x},
url = {https://europepmc.org/article/MED/42907852},
note = {CC BY},
}
RIS
TY - JOUR
TI - Plant-derived extracellular vesicles deliver spermidine to reprogram macrophage metabolism and ameliorate rheumatoid arthritis.
AU - Xiaocheng Wang
AU - Jiaxin He
AU - Yixiang Hong
AU - Xingyue Zeng
AU - Min Li
AU - Shixiong Cao
AU - Renge Liang
AU - Gengmin Zhou
AU - Qingwen Wang
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04836-x
UR - https://europepmc.org/article/MED/42907852
AB - Rheumatoid arthritis (RA) is driven by macrophage-mediated synovial inflammation closely linked to metabolic dysfunction, highlighting immunometabolism as a therapeutic target. Here, we engineered spermidine-loaded red cabbage-derived extracellular vesicles (RCEVs@SPD) as a plant-based nanoplatform to reprogram macrophage bioenergetics. In LPS-stimulated macrophages, RCEVs@SPD suppressed pro-inflammatory polarization and enhanced mitochondrial function, as evidenced by increased ATP production and mitochondrial membrane potential. Assay-based measurements further showed reduced extracellular acidification rate (ECAR) and elevated oxygen consumption rate (OCR), indicating a shift from glycolysis toward oxidative phosphorylation (OXPHOS). Untargeted LC-MS metabolomics revealed coordinated alterations in pathways supporting mitochondrial cofactor biosynthesis, redox balance, and central carbon metabolism. Transcriptomic analysis confirmed enrichment of OXPHOS and mitochondrial respiration gene signatures with concomitant repression of glycolytic programs and PI3K-AKT signaling. In vivo, RCEVs@SPD significantly alleviated collagen-induced arthritis, improved joint histopathology, and promoted anti‑inflammatory macrophage polarization. Notably, systemic macrophage depletion abolished the additional therapeutic benefit of RCEVs@SPD, demonstrating macrophage dependence. Collectively, these findings establish plant-derived extracellular vesicles as a biocompatible delivery system that potentiates spermidine to restore macrophage metabolic balance and mitigate RA pathology.
SN - 1477-3155
ER -