Zhou Long, Zhao Qingyu, Gu Lijuan, Tian Renfu, Li Yong, Xiong Xiaoxing
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Department of Neurosurgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei Province, China.
Mater Today Bio. 2025 Jun 7;33:101956. doi: 10.1016/j.mtbio.2025.101956. eCollection 2025 Aug.
Glioblastoma multiforme (GBM) is the most common and worst-prognosed primary malignant tumor in the central nervous system. Epithelial mesenchymal transition (EMT) is an important cause of postoperative invasion and recurrence in GBM. Due to the presence of the blood-brain barrier, local therapy may be the preferred route for treatment of GBM after surgery.
Our objective is to develop an anti- EMT functional hydrogel for post-GBM surgery tamponade. We fabricated self-assembled luteolin nanoparticles (LU NPs) via the solvent evaporation method, and characterized their morphology and particle size using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Furthermore, biological evaluations were conducted through CCK-8 assays, EdU staining, flow cytometry for cell cycle analysis, scratch assays, transwell assays and western blot. Ultimately, we constructed a polyvinyl alcohol (PVA) hydrogel loaded with luteolin nanoparticles and validated its therapeutic efficacy in vivo experiments.
We successfully synthesized LU NPs, which significantly inhibited GBM cell proliferation, as well as GBM cell invasion and migration in vitro. Furthermore, LU NPs downregulated the EMT signaling pathway. We discovered that the observed anti-tumor effects of LU NPs were dependent on the function of β-catenin. Additionally, we successfully constructed a PVA hydrogel loaded with LU NPs (LU@gel). Finally, in the postoperative model of intracranial GBM xenograft in mice, LU@gel effectively suppressed GBM proliferation and EMT, significantly prolonging the survival time of the mice.
In summary, we have demonstrated that LU@gel exhibits potent anti-GBM effects, primarily attributed to the inhibition of β-catenin-mediated cell proliferation and EMT.
多形性胶质母细胞瘤（GBM）是中枢神经系统中最常见且预后最差的原发性恶性肿瘤。上皮-间质转化（EMT）是GBM术后侵袭和复发的重要原因。由于血脑屏障的存在，局部治疗可能是GBM术后治疗的首选途径。
我们的目标是开发一种用于GBM术后填塞的抗EMT功能性水凝胶。我们通过溶剂蒸发法制备了自组装木犀草素纳米颗粒（LU NPs），并使用扫描电子显微镜（SEM）、透射电子显微镜（TEM）和动态光散射（DLS）对其形态和粒径进行了表征。此外，通过CCK-8测定、EdU染色、用于细胞周期分析的流式细胞术、划痕试验、Transwell试验和蛋白质免疫印迹进行生物学评估。最终，我们构建了负载木犀草素纳米颗粒的聚乙烯醇（PVA）水凝胶，并在体内实验中验证了其治疗效果。
我们成功合成了LU NPs，其在体外显著抑制GBM细胞增殖以及GBM细胞的侵袭和迁移。此外，LU NPs下调了EMT信号通路。我们发现观察到的LU NPs的抗肿瘤作用依赖于β-连环蛋白的功能。此外，我们成功构建了负载LU NPs的PVA水凝胶（LU@gel）。最后，在小鼠颅内GBM异种移植术后模型中，LU@gel有效抑制了GBM增殖和EMT，显著延长了小鼠的生存时间。
总之，我们已经证明LU@gel具有强大的抗GBM作用，主要归因于对β-连环蛋白介导的细胞增殖和EMT的抑制。
