Ferrocene-containing polymersome nanoreactors for synergistically amplified tumor-specific chemodynamic therapy
| Autor: | Jingbo Wang, Qinghao Zhou, Jean Felix Mukerabigwi, Yuheng Wang, Wendong Ke, Zhishen Ge, Shuang Zhang, Nannan Lu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Metallocenes
Pharmaceutical Science 02 engineering and technology Nanoreactor 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Neoplasms Tumor Microenvironment Humans Nanotechnology Prodrugs Glucose oxidase 030304 developmental biology 0303 health sciences biology Tumor hypoxia Hydrogen Peroxide Prodrug 021001 nanoscience & nanotechnology Combinatorial chemistry chemistry Polymersome biology.protein Hydroxyl radical Tirapazamine 0210 nano-technology Ethylene glycol |
| Zdroj: | Journal of Controlled Release. 333:500-510 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2021.04.007 |
| Popis: | Chemodynamic therapy (CDT) has been proposed to convert tumoral H2O2 into toxic hydroxyl radicals ( OH) via Fenton or Fenton-like reactions for antitumor efficacy, which is frequently limited by low H2O2 concentrations or lack of enough metal ions inside tumor tissues. In this report, we present ferrocene-containing responsive polymersome nanoreactors via loading glucose oxidase (GOD) and hypoxia-activable prodrug tirapazamine (TPZ) in the inner aqueous cavities. After intravenous injection, the polymersome nanoreactors with the optimized nanoparticle size of ~100 nm and poly(ethylene glycol) corona facilitate tumor accumulation. The tumor acidic microenvironment can trigger the permeability of the polymersome membranes to activate the nanoreactors and release the loaded TPZ prodrugs. Tumor oxygen and glucose can enter the polymersome nanoreactors and are transformed into H2O2 under the catalysis of GOD, which are further converted into OH via Fenton reaction under catalysis of ferrocene moieties. The oxygen consumption can aggravate tumor hypoxia to activate hypoxia-responsive TPZ prodrugs which can produce benzotriazinyl (BTZ) radicals and OH. All the produced radicals synergistically kill tumor cells via the amplified CDT and suppress the tumor growth efficiently. Thus, the ferrocene-containing responsive polymersome nanoreactors loading GOD and TPZ represent a potent nanoplatform to exert amplified CDT for improved anticancer efficacy. |
| Databáze: | OpenAIRE |
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