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 loca...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 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 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 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 levels.Our findings collectively indicate that LHN^(TMZ)+rutin is a promising biocompatible model for the local treatment of GB.展开更多
基金This study was supported by Scientific and Technological Research Council of Turkey(TUBITAK)under the Grant Number 121S624.
文摘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 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 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 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 levels.Our findings collectively indicate that LHN^(TMZ)+rutin is a promising biocompatible model for the local treatment of GB.
