A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber
Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber network (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol a...
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Elsevier
2024-12-01
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| Series: | Asian Journal of Pharmaceutical Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087624000886 |
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| author | Melis Ercelik Cagla Tekin Melisa Gurbuz Yagmur Tuncbilekli Hazal Yılmaz Dogan Busra Mutlu Pınar Eser Gulcin Tezcan Fatma Nur Parın Kenan Yildirim Mehmet Sarihan Gurler Akpinar Murat Kasap Ahmet Bekar Hasan Kocaeli Mevlut Ozgur Taskapilioglu Secil Ak Aksoy Rıfat Ozpar Bahattin Hakyemez Berrin Tunca |
| author_facet | Melis Ercelik Cagla Tekin Melisa Gurbuz Yagmur Tuncbilekli Hazal Yılmaz Dogan Busra Mutlu Pınar Eser Gulcin Tezcan Fatma Nur Parın Kenan Yildirim Mehmet Sarihan Gurler Akpinar Murat Kasap Ahmet Bekar Hasan Kocaeli Mevlut Ozgur Taskapilioglu Secil Ak Aksoy Rıfat Ozpar Bahattin Hakyemez Berrin Tunca |
| author_sort | Melis Ercelik |
| collection | DOAJ |
| description | Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber network (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHNTMZ and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHNTMZ+rutin, significantly reduced sphere size compared to untreated and LHNTMZ-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHNTMZ+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHNTMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHNTMZ+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHNTMZ+rutin is a promising biocompatible model for the local treatment of GB. |
| format | Article |
| id | doaj-art-768fed21c38445dea105c6734b0e0bec |
| institution | Kabale University |
| issn | 1818-0876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Asian Journal of Pharmaceutical Sciences |
| spelling | doaj-art-768fed21c38445dea105c6734b0e0bec2024-12-25T04:21:01ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762024-12-01196100971A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiberMelis Ercelik0Cagla Tekin1Melisa Gurbuz2Yagmur Tuncbilekli3Hazal Yılmaz Dogan4Busra Mutlu5Pınar Eser6Gulcin Tezcan7Fatma Nur Parın8Kenan Yildirim9Mehmet Sarihan10Gurler Akpinar11Murat Kasap12Ahmet Bekar13Hasan Kocaeli14Mevlut Ozgur Taskapilioglu15Secil Ak Aksoy16Rıfat Ozpar17Bahattin Hakyemez18Berrin Tunca19Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Metallurgical and Materials Engineering, Bursa Technical University, Bursa, TurkeyDepartment of Metallurgical and Materials Engineering, Bursa Technical University, Bursa, Turkey; Central Research Laboratory, Bursa Technical University, Bursa, TurkeyDepartment of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa, TurkeyDepartment of Polymer Materials Engineering, Faculty of Engineering and Natural Sciences, Bursa Technical University, Bursa, TurkeyDepartment of Polymer Materials Engineering, Faculty of Engineering and Natural Sciences, Bursa Technical University, Bursa, TurkeyDepartment of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, TurkeyDepartment of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, TurkeyDepartment of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, TurkeyDepartment of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, TurkeyDepartment of Neurosurgery, Faculty of Medicine, Istanbul Yeni Yuzyıl University, Istanbul, TurkeyInegol Vocation School, Bursa Uludag University, Bursa, TurkeyDepartment of Radiology, Faculty of Medicine, Bursa Uludağ University, Bursa, TurkeyDepartment of Radiology, Faculty of Medicine, Bursa Uludağ University, Bursa, TurkeyDepartment of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey; Corresponding author.Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber network (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHNTMZ and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHNTMZ+rutin, significantly reduced sphere size compared to untreated and LHNTMZ-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHNTMZ+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHNTMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHNTMZ+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHNTMZ+rutin is a promising biocompatible model for the local treatment of GB.http://www.sciencedirect.com/science/article/pii/S1818087624000886GlioblastomaLocal treatmentTemozolomideRutinHybrid layered composite nanofiber network |
| spellingShingle | Melis Ercelik Cagla Tekin Melisa Gurbuz Yagmur Tuncbilekli Hazal Yılmaz Dogan Busra Mutlu Pınar Eser Gulcin Tezcan Fatma Nur Parın Kenan Yildirim Mehmet Sarihan Gurler Akpinar Murat Kasap Ahmet Bekar Hasan Kocaeli Mevlut Ozgur Taskapilioglu Secil Ak Aksoy Rıfat Ozpar Bahattin Hakyemez Berrin Tunca A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber Asian Journal of Pharmaceutical Sciences Glioblastoma Local treatment Temozolomide Rutin Hybrid layered composite nanofiber network |
| title | A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber |
| title_full | A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber |
| title_fullStr | A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber |
| title_full_unstemmed | A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber |
| title_short | A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber |
| title_sort | new nano approach to prevent tumor growth in the local treatment of glioblastoma temozolomide and rutin loaded hybrid layered composite nanofiber |
| topic | Glioblastoma Local treatment Temozolomide Rutin Hybrid layered composite nanofiber network |
| url | http://www.sciencedirect.com/science/article/pii/S1818087624000886 |
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