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- W3165559956 abstract "Chemotherapy efficiency of platinum(II) (Pt(II)) is often attenuated owing to the low intracellular drugs concentration and glutathione (GSH)-mediated detoxification. To address these problems, we fabricated a step-by-step responsive nanogel (~160 nm) by copolymerization between four functional monomers. Hydrophilic methoxypolyethylene glycols (mPEG) distributed randomly on the surface of particles endowed the nanogel with “stealth” property in blood circulation, while the chemical crosslinking inside particles by platinum(IV) (Pt(IV)) linker remarkably increased the stability of nanogel in vivo. These advantages of nanogels leaded to higher accumulation at tumor region (6.4% ID/g), followed by triggering the dePEGylation effect by the cleavage of ortho ester at tumoral extracellular pH. Meanwhile, the exposed phenylboric acid (PBA) could significantly increase cellular uptake and intracellular drugs levels by targteing sialic acid residues on the cells membrane. More importantly, this nanogels could further deplete intracellular glutathione (GSH) by the dual-regulation of platinum(IV) and arylboronic ester, resulting in enhanced platinum(II) toxicity both in vitro and in vivo, eventually achieving superior inhibition rate (79.14%) in A549/DDP tumor. Thus, the sequentially responsive nanogel could be considered as an effective strategy for cancer treatment." @default.
- W3165559956 created "2021-06-07" @default.
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- W3165559956 date "2021-11-01" @default.
- W3165559956 modified "2023-10-14" @default.
- W3165559956 title "A sequentially responsive nanogel via Pt(IV) crosslinking for overcoming GSH-mediated platinum resistance" @default.
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- W3165559956 doi "https://doi.org/10.1016/j.jcis.2021.05.107" @default.
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