Antihepatoma Activity of Multifunctional Polymeric Nanoparticles Via Inhibition of Microtubules and Tyrosine Kinases

Abstract

Aim: Synthesis of poly-L-lactic acid nanoparticles comprising of microtubule-inhibitor docetaxel and tyrosine kinase inhibitor sorafenib (PLDS NPs) for hepatoma treatment. Materials & methods: PLDS NPs were prepared by the emulsion solvent evaporation method and the anticancer activity was evaluated in Huh7 hepatoma cells. Results: Real-time imaging of quantum dots incorporating poly-L-lactic acid nanoparticles showed a rapid internalization of the nanoparticles in Huh7 cells. PLDS NPs exerted stronger antiproliferative, apoptotic and antiangiogenic effects than free single drug counterparts. They strongly promoted microtubule bundling, multinucleation and increased mitotic index in Huh7 cells. They also inhibited the expression of pERK1/2, pAKT and cyclin D1. Conclusion: We developed a single-nanoscale platform for dual drug delivery and high-sensitivity quantum dots imaging for hepatoma treatment. [Formula: see text]

Comparative Analysis of the Cytotoxic Effect of a Complex of Selenium Nanoparticles Doped with Sorafenib, “Naked” Selenium Nanoparticles, and Sorafenib on Human Hepatocyte Carcinoma HepG2 Cells

“…The antitumor effect of So can also occur due to the inhibition of the RAF/MEK/ERK signaling cascade [ 31 ], which was also observed in our experiments, but with greater efficiency when using selenium nanoparticles. It has been shown on Huh7 hepatoma cells that the IC 50 for sorafenib in the efficiency of cell cycle arrest is 15 ± 1.4 µM, and for SeNPs it is 5 ± 2 µg/mL, while doping of SeNPs with sorafenib leads to a decrease in IC 50 to 820 ± 26 nM [ 34 ]. It was also shown on Huh7 cells that So in the effective concentration range of 15–30 μM causes a significant percentage of necrotic cell death (10.5–18%), while SeNPs at concentrations of 5–10 μg/mL are characterized by less pronounced necrosis (6–11%) [ 34 ].…”

“…It has been shown on Huh7 hepatoma cells that the IC 50 for sorafenib in the efficiency of cell cycle arrest is 15 ± 1.4 µM, and for SeNPs it is 5 ± 2 µg/mL, while doping of SeNPs with sorafenib leads to a decrease in IC 50 to 820 ± 26 nM [ 34 ]. It was also shown on Huh7 cells that So in the effective concentration range of 15–30 μM causes a significant percentage of necrotic cell death (10.5–18%), while SeNPs at concentrations of 5–10 μg/mL are characterized by less pronounced necrosis (6–11%) [ 34 ]. In our experiments, it was found that SeSo practically suppresses necrotic processes in HepG2 cells, predominantly causing apoptosis, especially at its early stages, at lower concentrations (for SeNPs, 2.5 µg/mL, for SeSo, 0.5 µg/mL).…”

Bio-Conjugated Quantum Dots for Cancer Research: Detection and Imaging

“…QDs-based signal probes are of great interest and have been tested in numerous biotechnological applications. Some of the early and most successful uses of QDs have been in immunofluorescence labeling of fixed cells and tissues (15,16), immuno-staining of membrane proteins (17,18), microtubules (19), nuclear antigens (20,21), and fluorescence in situ hybridization of chromosomes or combed DNA (22, 23) (Figure 3).…”