Enhanced Anti-Metastatic Activity of Etoposide Using Layered Double Hydroxide Nano Particles.
Cell migration and invasion are integral to lung cancer metastasis. In this study, we investigated the combination of traditional chemotherapy and a layered double hydroxide (LDH) carrier as a new strategy for the inhibition of migration and invasion. To investigate the characteristics and possible mechanisms of VP16-LDH [the Mg-Al/LDH containing etoposide (VP16)], we used several experimental techniques, such as transmission electron microscopy (TEM) and fluorescent microscopy. The TEM, X-ray diffraction (XRD) and zeta potential results indicated that VP16 binds well with LDH, with an average size of 70 nm, and the drug delivery system was confirmed to have the desired quality of slow release by the in vitro release test results. Fluorescent images showed that the cellular uptake of VP16-LDH was a caveolae-mediated and energy-dependent process. Moreover, A549 cells treated with VP16-LDH (5 μg/ml, 10 μg/ml) demonstrated significant inhibition of cell migration and invasion compared with the cells treated with free VP16 at the same concentration. The inhibition of AKT, mTOR and STAT3 phosphorylation and p-β-catenin up-regulation in VP16-LDH-treated cells revealed a possible molecular mechanism via the mTOR/AKT and STAT pathways, through which VP16-LDH had a stronger inhibitory effect on migration than the drug alone.
Yanjing
Y
Zhu
Youjun
Y
Wu
Haixia
H
Zhang
Zhaoqi
Z
Wang
Shilong
S
Wang
Yechang
Y
Qian
Rongrong
R
Zhu
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D005047:Etoposide / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006878:Hydroxides / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010316:Particle Size; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D004337:Drug Carriers; D006878:Hydroxides; D005047:Etoposide; C031356:hydroxide ion