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- W2314395576 abstract "Platinum(IV) prodrug diaminedichlorodihydroxyplatinum (ACHP) conjugated with a histone deacetylase (HDAC) inhibitor valproic acid (VA), VAAP, exhibited strong synergistic cytotoxicity, about 50–100 times more cytotoxic than ACHP or its simple mixture with VA, against various human carcinoma cell lines. VAAP could be quickly absorbed in the cell membrane and diffused into the cytosol. VAAP loaded in polyethylene glycol–polycaprolactone micelles (PEG-PCL) was taken up via endocytosis. The cytosolic VAAP was intracellular reduced to Pt(II) and released VA eliciting a HDAC inhibitory effect and subsequently induced cell cycle arrest at the S phase in 24 h and cell apoptosis in a time-dependent manner. The in vivo antitumor experiment on A549-xenograft tumor model showed that VAAP dispersed in Tween 80 or loaded in PEG-PCL nanoparticles had long blood circulation times and thereby high accumulation in tumors and exerted a significant in vivo inhibitory effect on tumor growth with low systemic toxicity. Therefore, this novel conjugate is very promising for cancer chemotherapy." @default.
- W2314395576 created "2016-06-24" @default.
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- W2314395576 date "2012-09-20" @default.
- W2314395576 modified "2023-10-10" @default.
- W2314395576 title "Conjugate of Pt(IV)–Histone Deacetylase Inhibitor as a Prodrug for Cancer Chemotherapy" @default.
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- W2314395576 doi "https://doi.org/10.1021/mp200597r" @default.
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