Redox-Sensitive Hydroxyethyl Starch-Doxorubicin Conjugate for Tumor Targeted Drug Delivery
| Autor: | Yihui Li, Zifu Li, Hang Hu, Huibi Xu, Yanxiao Ao, Qing Zhou, Xiangliang Yang, Chan Yu, Ying Wan |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Materials science
Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering 02 engineering and technology macromolecular substances Pharmacology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Drug Delivery Systems In vivo Cell Line Tumor Neoplasms polycyclic compounds medicine Humans General Materials Science Doxorubicin Cytotoxicity Chemistry organic chemicals technology industry and agriculture Starch Glutathione Prodrug 021001 nanoscience & nanotechnology 0104 chemical sciences carbohydrates (lipids) Drug delivery Molecular Medicine 0210 nano-technology Oxidation-Reduction Intracellular Conjugate medicine.drug |
| Zdroj: | ACS applied materialsinterfaces. 8(45) |
| ISSN: | 1944-8252 |
| Popis: | Doxorubicin (DOX) is one of the most potent anticancer agents in cancer chemotherapy, but the clinical use of DOX is restricted by its severe side effects caused by nonspecific delivery. To alleviate the side effects and improve the antitumor efficacy of DOX, a novel redox-sensitive hydroxyethyl starch-doxorubicin conjugate, HES-SS-DOX, with diameter of 19.9 ± 0.4 nm was successfully prepared for tumor targeted drug delivery and GSH-mediated intracellular drug release. HES-SS-DOX was relatively stable under extracellular GSH level (∼2 μM) but released DOX quickly under intracellular GSH level (2-10 mM). In vitro cell study confirmed the GSH-mediated cytotoxicity of HES-SS-DOX. HES-SS-DOX exhibited prolonged plasma half-life time and enhanced tumor accumulation in comparison to free DOX. As a consequence, HES-SS-DOX exhibited better antitumor efficacy and reduced toxicity as compared to free DOX in the in vivo antitumor activity study. The redox-sensitive HES-SS-DOX was proved to be a promising prodrug of DOX, with clinical potentials, to achieve tumor targeted drug delivery and timely intracellular drug release for effective and safe cancer chemotherapy. |
| Databáze: | OpenAIRE |
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