The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma
AbstractTemozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ....
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2022.2152911 |
| _version_ | 1797260970017423360 |
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| author | Haoyue Xu Yongkang Zhang Linfeng Li Yanhong Ren Feng Qian Lansheng Wang Hongwei Ma Ankang Quan Hongmei Liu Rutong Yu |
| author_facet | Haoyue Xu Yongkang Zhang Linfeng Li Yanhong Ren Feng Qian Lansheng Wang Hongwei Ma Ankang Quan Hongmei Liu Rutong Yu |
| author_sort | Haoyue Xu |
| collection | DOAJ |
| description | AbstractTemozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved. |
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| format | Article |
| id | doaj.art-e3fe945b662e44c1b0e9c54de47fea6a |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-04-24T23:33:46Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-e3fe945b662e44c1b0e9c54de47fea6a2024-03-15T14:22:18ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642023-12-0130111310.1080/10717544.2022.2152911The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in gliomaHaoyue Xu0Yongkang Zhang1Linfeng Li2Yanhong Ren3Feng Qian4Lansheng Wang5Hongwei Ma6Ankang Quan7Hongmei Liu8Rutong Yu9Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaInstitute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, ChinaAbstractTemozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved.https://www.tandfonline.com/doi/10.1080/10717544.2022.2152911Gliomadrug-resistancesiMGMTP(TMZ)n |
| spellingShingle | Haoyue Xu Yongkang Zhang Linfeng Li Yanhong Ren Feng Qian Lansheng Wang Hongwei Ma Ankang Quan Hongmei Liu Rutong Yu The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma Drug Delivery Glioma drug-resistance siMGMT P(TMZ)n |
| title | The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma |
| title_full | The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma |
| title_fullStr | The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma |
| title_full_unstemmed | The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma |
| title_short | The nanoprodrug of polytemozolomide combines with MGMT siRNA to enhance the effect of temozolomide in glioma |
| title_sort | nanoprodrug of polytemozolomide combines with mgmt sirna to enhance the effect of temozolomide in glioma |
| topic | Glioma drug-resistance siMGMT P(TMZ)n |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2022.2152911 |
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