期刊
BIOMACROMOLECULES
卷 15, 期 12, 页码 4534-4543出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm501338r
关键词
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资金
- Agence Nationale de la Recherche (ANR) [ANR-08-PCVI-030]
- Region Poitou-Charentes
- Ligue National Contre la Cancer
- Ligue Contre le Cancer
- Loire-Atlantique et Charente-Maritime
- Centre National de la Recherche Scientifique (CNRS)
- ARSMESO44
- Nantes University Hospital
- COST action [TD0905]
In vivo histone deacetylase (HDAC) inhibition by vorinostat under clinically acceptable dosing is limited by its poor pharmacokinetics properties. A new type of nontoxic pH-responsive delivery system has been synthesized by ring-opening metathesis polymerization, allowing for the selective distribution of vorinostat in mesothelioma tumors in vivo and subsequent histone reacetylation. The delivery system is synthesized by generic click chemistry, possesses native stealth properties for passive tumor targeting, and does not need additional chemistry for cellular internalization. Although vorinostat alone at 50 mg/kg in mice showed no effect, our new delivery system with 2 mg/kg vorinostat promoted histone reacetylation in tumors without side effects, demonstrating that our strategy improves the activity of this HDAC inihibitor in vivo.
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