Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of new linear iron chelators containing hydroxypyridinone and terephthalamide (TAMmeg) moieties have been prepared. All are hexadentate ligands composed of a systematically varied combination of methyl-3,2-hydroxypyridinone and 2,3-dihydroxyterephthalamide binding units; most are based on a spermidine scaffold, but one incorporates the bifunctional 2,3-dihydroxyterephthalamide unit as an integral part of the backbone. Protonation and ferric iron complex formation constants have been determined from solution thermodynamic studies, giving log beta(110) values of 25.7, 30.7, 36.3, 43.8, and 45.0, respectively. The ferric complexes display reversible reduction potentials from -276 to -1032 mV (measured relative to the normal hydrogen electrode) in alkaline solution. The incremental replacement of hydroxypyridinone units by terephthalamide binding groups progressively reduces the ligand acidity, markedly increases the iron-chelate stability, and improves the selectivity for the ferric ion over the ferrous ion. While the majority of iron chelators forming very stable ferric complexes are based on a tripodal backbone such as TREN, the ferric 5-LIO(TAMmeg)(2)(TAM) complex, despite its nontripodal scaffold, is one of the most stable iron complexes yet reported. Moreover, the high affinity for the ferric ion of the discussed linear ligands strongly correlates with their ability to remove iron in vivo.
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PMID:Synthesis and thermodynamic evaluation of mixed hexadentate linear iron chelators containing hydroxypyridinone and terephthalamide units. 1663 94

Immunotherapy has shown promising results in multiple malignancies. However, there are still significant challenges in cancer immunotherapy including the powerful immunosuppressive tumor microenvironment and adverse off-target side effects. Nanomaterials with defined physico-biochemical properties are versatile drug delivery platforms that may address these key technical challenges faced by cancer immunotherapy. Here, a tumor acidity-responsive biomacromolecule delivery system was designed to intratumorally deliver an immune-activating cytokine, macrophage colony-stimulating factor (M-CSF) and attenuate the acidic microenvironment. This nanoparticle was prepared by introducing CaCO3 as a crosslinker to form an M-CSF-loaded stable micelle (NP/M-CSF/CaCO3). Administration of NP/M-CSF/CaCO3 significantly inhibited tumor growth by enhancing T cell-mediated anti-tumor immune responses and reversing the TAM-mediated immunosuppression. This study provides new avenues for cascade amplification of the antitumor effects by targeting the tumor microenvironment. This approach may also help avoid unwanted complications.
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PMID:Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy. 3101 82