ArticleArthritis research & therapy2011
Treatment of experimental adjuvant arthritis with a novel folate receptor-targeted folic acid-aminopterin conjugate.
Article in Arthritis research & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 69 citations in OpenAlex.
- [ZIF-8@Pt Nanozyme Used for Scavenging Reactive Oxygen Species in the Treatment of Rheumatoid Arthritis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.Frontiers in immunology · 2024Article
- Targeting folate receptor beta on monocytes/macrophages renders rapid inflammation resolution independent of root causes.Cell reports. Medicine · 2021Article
- Targeted delivery of mPGES-1 inhibitors to macrophages via the folate receptor-β for inflammatory pain.Bioorganic & medicinal chemistry letters · 2021Article
- Article
- Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis.Journal of neuroinflammation · 2021Article
- Evaluation of the reducing potential of PSMA-containing endosomes by FRET imaging.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Depletion of activated macrophages with a folate receptor-beta-specific antibody improves symptoms in mouse models of rheumatoid arthritis.Arthritis research & therapy · 2019Article
- Folate receptor-beta expression as a diagnostic target in human & rodent nonalcoholic steatohepatitis.Toxicology and applied pharmacology · 2019Article
- The folate receptor β as a macrophage-mediated imaging and therapeutic target in rheumatoid arthritis.Drug delivery and translational research · 2019Review
- New Mechanism for Release of Endosomal Contents: Osmotic Lysis via Nigericin-Mediated KBioconjugate chemistry · 2018Article
- Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer.Beilstein journal of organic chemistry · 2018Article
- Imaging and Methotrexate Response Monitoring of Systemic Inflammation in Arthritic Rats Employing the Macrophage PET Tracer [Contrast media & molecular imaging · 2018Article
- FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer.Science translational medicine · 2017Article
- In-vivo monitoring of anti-folate therapy in arthritic rats using [Arthritis research & therapy · 2017Article
- Direct in vivo evidence of activated macrophages in human osteoarthritis.Osteoarthritis and cartilage · 2016Article
- Antiinflammatory Activity of a Novel Folic Acid Targeted Conjugate of the mTOR Inhibitor Everolimus.Molecular medicine (Cambridge, Mass.) · 2015Article
- Comparison of nanoparticle penetration into solid tumors and sites of inflammation: studies using targeted and nontargeted liposomes.Nanomedicine (London, England) · 2015Article
- Gene Expression Profiling in Peripheral Blood Cells and Synovial Membranes of Patients with Psoriatic Arthritis.PloS one · 2015Article
- Development of optical probes for in vivo imaging of polarized macrophages during foreign body reactions.Acta biomaterialia · 2014Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionFolate receptor (FR)-expressing macrophages have been shown to accumulate at sites of inflammation, where they promote development of inflammatory symptoms. To target such a macrophage population, we designed and evaluated the biologic activity of EC0746, a novel folic acid conjugate of the highly potent antifolate, aminopterin.
methodsUsing a FR-positive subclone of murine macrophage-derived RAW264.7 cells and rat thioglycollate-elicited macrophages, we studied the effect of EC0746 on dihydrofolate reductase activity, cell proliferation, and cellular response towards bacterial lipopolysaccharide as well as IFNγ activation. The EC0746 anti-inflammatory activity, pharmacokinetics, and toxicity were also evaluated in normal rats or in rats with adjuvant-induced arthritis; that is, a FR-positive macrophage model that closely resembles rheumatoid arthritis in humans.
resultsEC0746 suppresses the proliferation of RAW264.7 cells and prevents the ability of nonproliferating rat macrophages to respond to inflammatory stimuli. In the macrophage-rich rat arthritis model, brief treatment with subcutaneously administered EC0746 is shown to mediate an FR-specific anti-inflammatory response that is more potent than either orally administered methotrexate or subcutaneously delivered etanercept. More importantly, EC0746 therapy is also shown to be ~40-fold less toxic than unmodified aminopterin, with fewer bone marrow and gastrointestinal problems.
conclusionsEC0746 is the first high FR-binding dihydrofolate reductase inhibitor that demonstrates FR-specific anti-inflammatory activities both in vitro and in vivo. Our data reveal that a relatively toxic anti-inflammatory drug, such as aminopterin, can be targeted with folic acid to inflammatory macrophages and thereby relieve inflammatory symptoms with greatly reduced toxicity.
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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.