Band 5, Heft 4

Radioisotope therapy of cancer is on the rise applying mainly β-emitting radionuclides. However, due to exposure of healthy tissues, the maximum achievable radiation dose with these is limited. Auger-electron emitters (AEs) represent a promising alternative because of their mode of decay within a short nanometer range. The challenge is that their therapeutic efficacy relies on a close vicinity to DNA. To overcome this and to minimize toxicity, the construction of smart nanomedical devices is required, which ascertain tumor cell targeting with succeeding cellular uptake and nuclear translocation. In this review we describe the potential of AEs with focus on their delivery down to the DNA level and their cellular effects. Reported efforts comprise different tumor-targeting strategies, including the use of antibodies or peptides with nuclear localizing sequences. Recently, attention has shifted to various nanoparticle formats for overcoming delivery problems. To this end, these approaches have mostly been tested in cell lines in vitro applying AEs more suited for imaging than therapy. This defines a demand for nanomedical formulations with documented in vivo activity, using AEs selected for their therapeutic potential to come closer to real clinical settings.

Lung cancer is a major and increasing global health problem. While there have been significant advances in the understanding of lung cancer biology, still no current therapy exists to reduce the inevitable and lethal progression of this disease. Silver nanowires (AgNWs) are promising candidates for a wide range of biomedical applications and the treatment of life-threatening diseases due to their unique physico-chemical and biochemical properties. However, the safety of this nanomaterial and its use as a biomedical tool are still under debate. This study evaluates the in vitro internalisation, cytotoxicity and influence on the cell cycle of AgNWs in lung adenocarcinoma (A549) cells and lung normal fibroblasts (MRC-5 cells). Our results demonstrate that AgNWs could be internalised effectively into A549 and MRC-5 cells without inducing detectable cytotoxicity, thus providing preliminary evidence on the future potential of AgNWs as biocompatible drug delivery platforms applicable in lung cancer therapies.

The ability to efficiently transfect plasmid DNA (pDNA) into eukaryotic cells has exerted major impact on scientific research in recent years, and translation to clinical application is ongoing, but challenging. In addition to the choice of the delivery vector, the topology of the DNA seems to be a key factor for efficient transfection. The nanostructured DNA/Vector complexes may differ in size, charge, and shape, for example. This study therefore investigated the transfection efficiency of circular versus linearized plasmid DNA using a GFP expressing vector with Lipofectamine2000 and linear 25 kDA polyethylenimine (PEI). Transfection efficiency and cytotoxicity were measured by flow cytometry and fluorescence microscopy. Shape was determined by transmission electron microscopy. Transfection agent concentrations were chosen below the toxicity level. We determined the optimal N/P ratio over 48 h by using two different concentrations of plasmid DNA. With the increase of DNA concentration and increasing N/P ratio, transfection efficiency also increased. Our results showed a better transfection efficiency with the circular compared to the linearized DNA, under the same experimental conditions for both Lipofectamine and PEI. In electron microscopy, there was a notable difference in the shape of the complexes: circular DNA had random coil appearance in well compacted, roughly spherical shape, while linearized DNA appeared as worm-like strands, both, when complexed with Lipofectamine or with polyethyleneimine. This generates the hypothesis that the shape of the transfection particle may be an important factor for successful gene transfer.