Stepwise-activatable hypoxia triggered nanocarrier-based photodynamic therapy for effective synergistic bioreductive chemotherapy
| Autor: | Yi Liu, Li Wang, Wei Jiang, Yangyang Zhao, Bejjanki Naveen Kumar, Hang Liu, Khan Malik Ihsanullah, Hassan Muhammad |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_treatment
Cell Biophysics Bioengineering Photodynamic therapy 02 engineering and technology Biomaterials 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor medicine Humans Photosensitizer Hypoxia 030304 developmental biology 0303 health sciences Tumor microenvironment Photosensitizing Agents Prodrug 021001 nanoscience & nanotechnology Cell Hypoxia medicine.anatomical_structure Photochemotherapy chemistry Mechanics of Materials Drug delivery Ceramics and Composites Cancer research Nanoparticles Tirapazamine Nanocarriers 0210 nano-technology |
| Zdroj: | Biomaterials. 245:119982 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2020.119982 |
| Popis: | Tumor cell populations are highly heterogeneous, which limit the homogeneous distribution and optimal delivery of nanomedicines, thereby inducing insufficient therapeutic benefits. We develop tumor microenvironment activatable and external stimuli-responsive drug delivery system (TAT+AzoNPs), which can improve photodynamic therapy (PDT) induced bioreductive chemotherapy in different tumor cells both proximal and distal to vessels. The TAT peptide on the surface of TAT+AzoNPs can both facilitate the cell uptake and the penetration of TAT+AzoNPs, owing to its responsiveness to tumor stimuli pH. TAT+AzoNPs can keep the cargoes (photosensitizer chlorine e6 (Ce6) and hypoxia activatable prodrug tirapazamine (TPZ)) and highly accumulate within tumor cells proximity and distal to vessels. The Azo-benzene bonds as the linkers between amphiphilic polymers remain stable under normoxia, but quite break at hypoxic conditions. Upon external laser irradiation, the intratumoral fate of TAT+AzoNPs involved two processes: 1) TAT+AzoNPs achieve efficient PDT on tumor cells proximal to vessel, since sufficient O2 supply; and 2) PDT-induced more hypoxia can trigger TPZ release by breakage of Azo-benzene bond as well as accelerate the activation of TPZ for improvingcombination therapy efficacy in tumor cells distal to vessel. This study gives a direction for the development of stepwise-activatable hypoxia triggered nanosystem for PDT-induced bioreductive chemotherapy for tumor cells in different distances to vessels. |
| Databáze: | OpenAIRE |
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