Inhibitory Effect of Poly(lactic-co-glycolic acid) Nanoparticles Loaded with Resveratrol and Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN) siRNA on Lung Cancer Cells

Abstract

More than 50% of patients with Non-small-cell lung carcinoma (NSCLC) develop metastasis after diagnosis, and only 14% of patients survive for more than 5 years. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are characterized by good stability and long vascular circulation time, and are particularly suitable for passive targeted treatment of tumors. Resveratrol (Res) can prevent normal cell carcinogenesis, inhibit the spread of cancer cells and cause cancer cell apoptosis. However, the use of resveratrol has been limited because of low bioavailability and short half-life. We in this study intended to find a highly specific nano-delivery system to enhance the therapeutic effect against tumors through carrying chemotherapeutic drugs and siRNA. PLGApolyethylene imine (PEI) nanoparticles co-delivered by resveratrol and PTEN siRNA were prepared. Oregon Green and Cy5 were used to label resveratrol and siRNA PTEN, respectively, and characterized by electron microscopy. Then, the nanoparticles were used to treat lung cancer cells. Western Blot analyzed the effects of nanoparticles on related proteins, and we used the CCK8 assay analyze the cytotoxicity of nanoparticles. Results showed that, the size of spherical PLGA NPs was about 80 nm, and the size of NPs increased significantly after attaching PEI to PLGA NPs or PLGA-PEI NPs carried PTEN siRNA. When PTEN expression was inhibited, resveratrol toxicity on lung cancer cells was increased. A549 and A549/T12 cells showed more sensitive to resveratrol loaded PLGA NPs than to resveratrol free NPs alone. The results also demonstrated that the nanoparticles loaded resveratrol increased the cancer cell toxicity of resveratrol. In addition, the PLGA-PEI nanoparticles co-delivered by resveratrol and PTEN siRNA can suppress tumor cells proliferation by inhibiting the expression of PTEN. In this study, PLGA-PEI-RES-PTEN nanocomplex was synthesized by solvent free evaporation and stabilizer free method. The complex can be absorbed by cancer cells, down-regulate PTEN protein, and effectively damage lung cancer cells.