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- W2070762445 abstract "Water soluble poly(ethylene oxide)-graft-methotrexate (PEO-g-MTX) conjugates with a robust amide linkage via the amine or carboxylic acid groups of MTX were designed, prepared and investigated for in vitro anti-tumor effects. MTX was conjugated to multi-functional PEO containing multiple pendant carboxylic acid (PEO-g-COOH) or amine groups (PEO-g-NH2) via the carbodiimide chemistry, which afforded PEO-g-MTX conjugates with an amide bond to the aminopteridine ring or carboxylic acid groups of MTX (denoted as PEO-g-MTX(COOH) and PEO-g-MTX(NH2), respectively). Dynamic light scattering (DLS) revealed that all PEO-g-MTX conjugates, with MTX contents varying from 4.8 to 19.6 wt%, existed as unimers in phosphate buffer (PB, pH 7.4, 20 mmol·L−1). Interestingly, MTT assays showed that PEO-g-MTX(COOH) exhibited potent anti-tumor activity in HeLa, A549, KB and NIH3T3 cells with cytotoxicity profiles comparable to that of free MTX. In contrast, PEO-g-MTX(NH2) revealed diminishing cytostatic effect with IC50 (half maximal inhibitory concentration) ten to hundred times higher than that of PEO-g-MTX(COOH). Moreover, PEO-g-MTX(COOH) conjugates allowed facile conjugation with targeting ligands. Notably, folate-decorated PEO-g-MTX(COOH) macromolecular drugs showed apparent targetability to folate receptor-overexpressing KB cells with an IC50 over 12-fold lower than non-targeting PEO-g-MTX(COOH) control and about 2-fold lower than free MTX under otherwise the same conditions." @default.
- W2070762445 created "2016-06-24" @default.
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- W2070762445 date "2013-11-04" @default.
- W2070762445 modified "2023-09-24" @default.
- W2070762445 title "Poly(ethylene oxide)-graft-methotrexate Macromolecular Drugs Conjugating via Aminopteridine Ring Exhibit Potent Anticancer Activity" @default.
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- W2070762445 doi "https://doi.org/10.1002/cjoc.201300611" @default.
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