PEGylated graphene oxide as a nanocarrier of the disulfide prodrug of podophyllotoxin for cancer therapy
Abstract Efficient drug delivery systems are required to increase drug concentrations at tumor sites and to reduce the side effects on normal cells. In this work, we developed a nanoscale drug delivery system based on graphene oxide (GO) and used it to load a disulfide prodrug of podophyllotoxin (DCM-S-PPT), which was linked by a thiol-specific cleavable disulfide bond. In order to improve the biocompatibility in physiological solution, GO was functionalized with 6-armed polyethylene glycol (PEG) and characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. By atomic force microscopy, the size distribution of the nanoparticles was shown to be 25~250 nm. DCM-S-PPT was loaded on GO-PEG via p–p stacking and hydrophobic interactions. The loading rate reached 138%. In vitro cytotoxicity assay showed that GO-PEG/DCM-S-PPT inhibited the proliferation of human cervical adenocarcinoma HeLa cells more than that of human normal kidney 293T cells, which was attributed to the different intracellular concentrations of GSH. After intravenous injection in mice bearing tumors, GO-PEG/DCM-S-PPT showed the better antitumor activity and less side effects than those of DCM-S-PPT and PPT. Compared with DCM-S-PPT or PPT, GO-PEG/DCM-S-PPT complex showed the best tumor-targeting and specific drug release. Our results provide a novel strategy for the combination of nanocarriers and modified chemotherapy drugs in the future..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Journal of nanoparticle research - 22(2020), 9 vom: 12. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yajing [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
| doi: |
10.1007/s11051-020-05003-5 |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract Efficient drug delivery systems are required to increase drug concentrations at tumor sites and to reduce the side effects on normal cells. In this work, we developed a nanoscale drug delivery system based on graphene oxide (GO) and used it to load a disulfide prodrug of podophyllotoxin (DCM-S-PPT), which was linked by a thiol-specific cleavable disulfide bond. In order to improve the biocompatibility in physiological solution, GO was functionalized with 6-armed polyethylene glycol (PEG) and characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. By atomic force microscopy, the size distribution of the nanoparticles was shown to be 25~250 nm. DCM-S-PPT was loaded on GO-PEG via p–p stacking and hydrophobic interactions. The loading rate reached 138%. In vitro cytotoxicity assay showed that GO-PEG/DCM-S-PPT inhibited the proliferation of human cervical adenocarcinoma HeLa cells more than that of human normal kidney 293T cells, which was attributed to the different intracellular concentrations of GSH. After intravenous injection in mice bearing tumors, GO-PEG/DCM-S-PPT showed the better antitumor activity and less side effects than those of DCM-S-PPT and PPT. Compared with DCM-S-PPT or PPT, GO-PEG/DCM-S-PPT complex showed the best tumor-targeting and specific drug release. Our results provide a novel strategy for the combination of nanocarriers and modified chemotherapy drugs in the future. | ||
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| 700 | 1 | |a Huang, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Ping |e verfasserin |4 aut | |
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