A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber

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dc.authorid0000-0002-1640-6035
dc.authorid0000-0002-3760-9755
dc.authorid0000-0003-1359-4445
dc.contributor.authorErcelik, Melis
dc.contributor.authorTekin, Cagla
dc.contributor.authorGurbuz, Melisa
dc.contributor.authorTuncbilekli, Yagmur
dc.contributor.authorDogan, Hazal Yilmaz
dc.contributor.authorMutlu, Busra
dc.contributor.authorTunca, Berrin
dc.date.accessioned2026-02-08T15:15:07Z
dc.date.available2026-02-08T15:15:07Z
dc.date.issued2024
dc.departmentBursa Teknik Üniversitesi
dc.description.abstractTotal 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 mesh (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-gamma, 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. (c) 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
dc.description.sponsorshipCouncil of Higher Education (CoHE); Scientific and Technological Research Council of Turkey (TUBITAK) [121S624]
dc.description.sponsorshipThis study represents a part of Melis Ercelik's doctoral thesis research at Bursa Uludag University, Department of Medical Biology. The author Melis Ercelik is granted by 100/2000 The Council of Higher Education (CoHE) as a PhD Scholar in Molecular Biology and Genetics (Gene Therapy and Genome Studies) . We greatly acknowledge to the Scientific and Technological Research Council of Turkey (TUBITAK) for supporting author Melis Ercelik within the scope of the 2211- C priority areas doctoral program scholarship. We greatly acknowledge to the Scientific and Technological Research Council of Turkey (TUBITAK) for supporting author Cagla Tekin within the scope of the 2211-A doctoral program scholarship. Special thanks to Dr. Tugba Bagci Onder from Koc University, for kindly providing the GB cell line. We thanks to Prof. Dr. S , uekrue Y & imath;ld & imath;r & imath;m from Istanbul Maltepe University for his support in IHC analysis and Prof. Dr. Tuelin Alkan from Bursa Uludag University for sharing the supplementary material in vivo experiments with us. We would also like to thanks to MRI technician Senem Elber (magnetic resonance imaging technologist) for special assistance with in vivo imaging. This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) under the Grant Number 121S624. The authors thank to TUBITAK for their supports.
dc.identifier.doi10.1016/j.ajps.2024.100971
dc.identifier.issn1818-0876
dc.identifier.issue6
dc.identifier.pmid39640055
dc.identifier.scopus2-s2.0-85209663391
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ajps.2024.100971
dc.identifier.urihttps://hdl.handle.net/20.500.12885/5613
dc.identifier.volume19
dc.identifier.wosWOS:001365143700001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherShenyang Pharmaceutical Univ
dc.relation.ispartofAsian Journal of Pharmaceutical Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzWOS_KA_20260207
dc.subjectGlioblastoma
dc.subjectLocal treatment
dc.subjectTemozolomide
dc.subjectRutin
dc.subjectHybrid layered composite nanofiber
dc.subjectweb
dc.titleA new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber
dc.typeArticle

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