Almost 10 years ago, an eleventh protein of influenza A viruses was discovered in a search for CD8+ T-cell epitopes. This protein was named PB1-F2 since it is encoded in the +1 reading frame of the PB1 gene segment. Various studies have shown that PB1-F2 has a pleiotropic effect: (1) The protein can induce apoptosis in a cell type-dependent manner, (2) PB1-F2 is able to promote inflammation, and (3) finally it up-regulates viral polymerase activity by its interaction with the PB1 subunit. These properties could contribute to an enhanced pathogenicity. However, the underlying mechanism is not fully understood yet. New data suggest that some effects of PB1-F2 are strain-specific and host-specific.

Localized magnetic heating treatments (hyperthermia, thermal ablation) using superparamagnetic iron oxide nanoparticles continue to be an active area of cancer research. The present study uses magnetic nanoparticles (MNP) as bimodal tools and combines magnetically induced cell labelling and magnetic heating. The main focus was to assess if a selective and higher MNP accumulation within tumour cells due to magnetic labelling (max. 56 and 83 mT) and consequently a larger heating effect occurs after exposure to an alternating magnetic field (magnetic heating: frequency 400 kHz, amplitude 24.6 kA m−1) in order to eliminate labelled tumour cells effectively. The results demonstrate that the magnetically based cellular MNP uptake by human adenocarcinoma cells is due to suitable magnetic field gradients in vitro which intensify the temperature increase generated during magnetic heating. A significantly (P≤0.05) enhanced MNP cell uptake due to 83 mT labelling compared to controls or to 56 mT labelling was observed. Our experiments required the following conditions, namely a cell concentration of 2.5 × 107 cells ml−1, a minimum MNP concentration of 0.32 mg Fe ml−1 culture medium, and an incubation time of 24 h, to reach this effect as well as for the significantly enlarged heating effects to occur.

Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells.