Curcumin-Loaded Layered Double Hydroxide Nanoparticles-Induced Autophagy for Reducing Glioma Cell Migration and Invasion.

Glioblastoma is difficult to cure due to the high risks of invasion and metastasis. Although curcumin has shown beneficial effects against malignant glioma cells, its poor properties have limited its application. The aim of this study was to design a nanocarrier for curcumin to exert sufficient anti-migration and anti-invasion effects on A172 cells. Curcuminloaded layered double hydroxide nanoparticles (Cur/LDH NPs) were synthesized, and the physicochemical properties were characterized using transmission electron microscopy (TEM), zeta potential, Fourier transform infrared spectrometry (FTIR) and X-ray powder diffraction (XRD). Then, Cur/LDH NPs were applied to A172 cells to assess the anti-migration and anti-invasion effects, cellular uptake, autophagy activity, and the related mechanisms. The prepared Cur/LDH NPs were 119±34 nm in size and exhibited a drug-loading efficiency of 21.31±1.83%. Compared with LDH and Cur alone, the Cur/LDH NPs significantly reduced cell migration and invasion when applied at low doses (0.1 and 0.5 μg/ml), and these effects were associated with a down-regulation of PI3K/AKT/mTOR signaling pathway. The Cur/LDH NPs were easily taken up by A172 cells and were mainly located in lysosomes and mitochondria in a time-dependent manner. Importantly, autophagy, which can be triggered by the inhibition of mTOR and by nanomaterials, was detected distinctly in A172 cells exposed to Cur/LDH NPs via the autophagic marker LC3A/B. In addition, the expression levels of Atg5-Atg12 and LAMP-1 were increased in the Cur/LDH NPs groups, and autophagic vacuoles were observed via TEM. Our work suggests that autophagy can promote the anti-migration and anti-invasion effects of Cur/LDH NPs against glioblastoma.