Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle
Glioblastoma multiforme (GBM) has remained one of the most lethal and <i>challenging</i> cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index:...
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2021-05-01
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| author | Tao-Chieh Yang Shih-Jung Liu Wei-Lun Lo Shu-Mei Chen Ya-Ling Tang Yuan-Yun Tseng |
| author_facet | Tao-Chieh Yang Shih-Jung Liu Wei-Lun Lo Shu-Mei Chen Ya-Ling Tang Yuan-Yun Tseng |
| author_sort | Tao-Chieh Yang |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) has remained one of the most lethal and <i>challenging</i> cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in <i>irinotecan can induce toxicities that</i> outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM. |
| first_indexed | 2024-03-10T11:05:11Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:05:11Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3554fb60a2e04abd8d20265cd4bf200b2023-11-21T21:11:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012211555710.3390/ijms22115557Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric MicroparticleTao-Chieh Yang0Shih-Jung Liu1Wei-Lun Lo2Shu-Mei Chen3Ya-Ling Tang4Yuan-Yun Tseng5Department of Neurosurgery, School of Medicine, Chung Shan Medical University Hospital, Taichung 40201, TaiwanDepartment of Mechanical Engineering, Chang Gung University, Taoyuan 33302, TaiwanDivision of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, TaiwanDepartment of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110301, TaiwanDepartment of Mechanical Engineering, Chang Gung University, Taoyuan 33302, TaiwanDivision of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235041, TaiwanGlioblastoma multiforme (GBM) has remained one of the most lethal and <i>challenging</i> cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in <i>irinotecan can induce toxicities that</i> outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.https://www.mdpi.com/1422-0067/22/11/5557glioblastoma multiforme (GBM)SN-38interstitial chemotherapytemozolomide-resistancepoly[(d,l)-lactide-co-glycolide] (PLGA) |
| spellingShingle | Tao-Chieh Yang Shih-Jung Liu Wei-Lun Lo Shu-Mei Chen Ya-Ling Tang Yuan-Yun Tseng Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle International Journal of Molecular Sciences glioblastoma multiforme (GBM) SN-38 interstitial chemotherapy temozolomide-resistance poly[(d,l)-lactide-co-glycolide] (PLGA) |
| title | Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle |
| title_full | Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle |
| title_fullStr | Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle |
| title_full_unstemmed | Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle |
| title_short | Enhanced Anti-Tumor Activity in Mice with Temozolomide-Resistant Human Glioblastoma Cell Line-Derived Xenograft Using SN-38-Incorporated Polymeric Microparticle |
| title_sort | enhanced anti tumor activity in mice with temozolomide resistant human glioblastoma cell line derived xenograft using sn 38 incorporated polymeric microparticle |
| topic | glioblastoma multiforme (GBM) SN-38 interstitial chemotherapy temozolomide-resistance poly[(d,l)-lactide-co-glycolide] (PLGA) |
| url | https://www.mdpi.com/1422-0067/22/11/5557 |
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