[show abstract][hide abstract] ABSTRACT: Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.
[show abstract][hide abstract] ABSTRACT: We studied the toxicity of ZnO nanomaterials in terms of physicochemical characteristics and reactive oxygen species (ROS) properties. ZnO nanorods [synthesized at room temperature (ZnO-RT, length; 18.0±4.2 nm) and at 60 °C (ZnO-60, length; 80.5±6.8 nm)] were used to evaluate the potential toxicity upon growth velocity-related particle size. The cytotoxicity of ZnO-60 was higher than that of ZnO-RT. We observed that the toxicity of ZnO-RT and ZnO-60 was related with ROS formation by using antioxidant N-acetylcysteine and electron spin resonance. Also, we found that the source of toxicity was not related to Zn(2+) ions released from ZnO in 24h treatment. Our results indicate that toxicity of ZnO nanorods is caused by the amounts of ROS. Our study strongly suggests that size of nanomaterial is not the sole factor to be considered, thus, the development of appropriate criteria based on morphological/physicochemical characteristics as well as synthesis procedures is needed to evaluate the precise toxicity.