Application of PVA hydrogel loaded with luteolin nanoparticles in anti EMT treatment after GBM

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.