ArticleACS nano2014
Fumagillin prodrug nanotherapy suppresses macrophage inflammatory response via endothelial nitric oxide.
Article in ACS nano, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Advances in the research of the role of macrophage/microglia polarization-mediated inflammatory response in spinal cord injury.Frontiers in immunology · 2022Pooled it
- A Dual-Pronged Hafnia-Prodrug-Lipid Nanoplatform Coupling Radiosensitization and DNA Homologous Recombination Inhibition.ACS nano medicine · 2026Article
- Sustained monocyte activation by persistent challenges with either oxLDL or free cholesterol and underlying mechanisms.ImmunoHorizons · 2026Article
- Engineering nanoparticles for macrophage reprogramming in chronic inflammatory diseases: current advances, challenges, and future perspectives.Frontiers in bioengineering and biotechnology · 2026Review
- Angiogenesis in rheumatoid Arthritis: Pathological characterization, pathogenic mechanisms, and nano-targeted therapeutic strategies.Bioactive materials · 2025Review
- Methionine Aminopeptidase 2 (MetAP2) Inhibitor BL6 Attenuates Inflammation in Cultured Microglia and in a Mouse Model of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Article
- Intrathecal Fumagillin Alleviates Chronic Neuropathy-Induced Nociceptive Sensitization and Modulates Spinal Astrocyte-Neuronal Glycolytic and Angiogenic Proteins.Molecular neurobiology · 2025Article
- Research Progress in Mutagenesis Techniques forMini reviews in medicinal chemistry · 2025Review
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
- Recent Advances in Anti-Atherosclerosis and Potential Therapeutic Targets for Nanomaterial-Derived Drug Formulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Nitric Oxide: Physiological Functions, Delivery, and Biomedical Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Nanomedicine-based multimodal therapies: Recent progress and perspectives in colon cancer.World journal of gastroenterology · 2023Review
- Tat-NTS peptide protects neurons against cerebral ischemia-reperfusion injury via ANXA1 SUMOylation in microglia.Theranostics · 2023Article
- Article
- Nanoparticle encapsulated CQ/TAM combination harmonizes with MSCs in arresting progression of severity in AP mice through iNOS (IDO) signaling.Materials today. Bio · 2022Article
- Near-infrared light-triggered nano-prodrug for cancer gas therapy.Journal of nanobiotechnology · 2021Review
- Tailoring Materials for Modulation of Macrophage Fate.Advanced materials (Deerfield Beach, Fla.) · 2021Review
- Nanomaterials Manipulate Macrophages for Rheumatoid Arthritis Treatment.Frontiers in pharmacology · 2021Review
- Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine.Particle and fibre toxicology · 2020Review
- The Role of Autophagy and Mitophagy in Bone Metabolic Disorders.International journal of biological sciences · 2020Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Antiangiogenesis has been extensively explored for the treatment of a variety of cancers and certain inflammatory processes. Fumagillin, a mycotoxin produced by Aspergillus fumigatus that binds methionine aminopeptidase 2 (MetAP-2), is a potent antiangiogenic agent. Native fumagillin, however, is poorly soluble and extremely unstable. We have developed a lipase-labile fumagillin prodrug (Fum-PD) that eliminated the photoinstability of the compound. Using αvβ3-integrin-targeted perfluorocarbon nanocarriers to deliver Fum-PD specifically to angiogenic vessels, we effectively suppressed clinical disease in an experimental model of rheumatoid arthritis (RA). The exact mechanism by which Fum-PD-loaded targeted nanoparticles suppressed inflammation in experimental RA, however, remained unexplained. We herein present evidence that Fum-PD nanotherapy indirectly suppresses inflammation in experimental RA through the local production of endothelial nitric oxide (NO). Fum-PD-induced NO activates AMP-activated protein kinase (AMPK), which subsequently modulates macrophage inflammatory response. In vivo, NO-induced AMPK activation inhibits mammalian target of rapamycin (mTOR) activity and enhances autophagic flux, as evidenced by p62 depletion and increased autolysosome formation. Autophagy in turn mediates the degradation of IkappaB kinase (IKK), suppressing the NF-κB p65 signaling pathway and inflammatory cytokine release. Inhibition of NO production by N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, reverses the suppression of NF-κB-mediated inflammatory response induced by Fum-PD nanotherapy. These unexpected results uncover an activity of Fum-PD nanotherapy that may be further explored in the treatment of angiogenesis-dependent diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.