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

Autor:	Ercelik M; Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Tekin C; Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Gurbuz M; Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Tuncbilekli Y; Department of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Dogan HY; Department of Metallurgical and Materials Engineering, Bursa Technical University, Bursa, Turkey., Mutlu B; Department of Metallurgical and Materials Engineering, Bursa Technical University, Bursa, Turkey.; Central Research Laboratory, Bursa Technical University, Bursa, Turkey., Eser P; Department of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Tezcan G; Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa, Turkey., Parın FN; Department of Polymer Materials Engineering, Faculty of Engineering and Natural Sciences, Bursa Technical University, Bursa, Turkey., Yildirim K; Department of Polymer Materials Engineering, Faculty of Engineering and Natural Sciences, Bursa Technical University, Bursa, Turkey., Sarihan M; Department of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, Turkey., Akpinar G; Department of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, Turkey., Kasap M; Department of Medical Biology/Proteomics Laboratory, Kocaeli University, Kocaeli, Turkey., Bekar A; Department of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Kocaeli H; Department of Neurosurgery, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey., Taskapilioglu MO; Department of Neurosurgery, Faculty of Medicine, Istanbul Yeni Yuzyıl University, Istanbul, Turkey., Aksoy SA; Inegol Vocation School, Bursa Uludag University, Bursa, Turkey., Ozpar R; Department of Radiology, Faculty of Medicine, Bursa Uludağ University, Bursa, Turkey., Hakyemez B; Department of Radiology, Faculty of Medicine, Bursa Uludağ University, Bursa, Turkey., Tunca B; Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.
Jazyk:	angličtina
Zdroj:	Asian journal of pharmaceutical sciences [Asian J Pharm Sci] 2024 Dec; Vol. 19 (6), pp. 100971. Date of Electronic Publication: 2024 Oct 23.
DOI:	10.1016/j.ajps.2024.100971
Abstrakt:	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 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 LHN TMZ and LHN rutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHN TMZ +rutin , significantly reduced sphere size compared to untreated and LHN TMZ -treated cells ( P < 0.0001). In an orthotopic C6-induced GB rat model, LHN TMZ +rutin therapy demonstrated a more pronounced tumor-reducing effect than LHN TMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHN TMZ +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 LHN TMZ +rutin is a promising biocompatible model for the local treatment of GB. Competing Interests: The authors declare no conflicts of interest. (© 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V.)
Databáze:	MEDLINE
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