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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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Asian Journal of Pharmaceutical Sciences 2024年第6期19卷 101-122页

作者： 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 Department of Medical Biology Faculty of MedicineBursa Uludag UniversityBursaTurkey Department of Neurosurgery Faculty of MedicineBursa Uludag UniversityBursaTurkey Department of Metallurgical and Materials Engineering Bursa Technical UniversityBursaTurkey Central Research Laboratory Bursa Technical UniversityBursaTurkey Department of Fundamental Sciences Faculty of DentistryBursa Uludag UniversityBursaTurkey Department of Polymer Materials Engineering Faculty of Engineering and Natural SciencesBursa Technical UniversityBursaTurkey Department of Medical Biology/Proteomics Laboratory Kocaeli UniversityKocaeliTurkey Department of Neurosurgery Faculty of MedicineIstanbul Yeni Yuzyıl UniversityIstanbulTurkey Inegol Vocation School Bursa Uludag UniversityBursaTurkey Department of Radiology Faculty of MedicineBursa Uludag UniversityBursaTurkey

Total resection of glioblastoma(GB)tumors is nearly impossible,and systemic administration of temozolomide(TMZ)is often *** study presents a hybrid layered composite nanofiber network(LHN)designed for localized treatment in GB tumor *** LHN,consisting of polyvinyl alcohol and core-shell polylactic acid layers,was loaded with TMZ and *** vitro analysis revealed that LHN^(TMZ) and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells,while the combination,LHN^(TMZ)+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 *** volume,assessed by magnetic resonance imaging,was significantly reduced in LHN^(TMZ)+rutin-treated rats compared to untreated *** 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 ***,the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic *** was evidenced by a decrease in the angiogenesismarker 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 *** findings collectively indicate that LHN^(TMZ)+rutin is a promising biocompatible model for the local treatment of GB.

关键词： Glioblastoma Local treatment Temozolomide Rutin Hybrid layered composite nanofiber network

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