In vitro bio-functionality of gallium nitride sensors for radiation biophysics.

There is an increasing interest in the integration of hybrid bio-semiconductor systems for the non-invasive evaluation of physiological parameters. High quality gallium nitride and its alloys show promising characteristics to monitor cellular parameters. Nevertheless, such applications not only request appropriate sensing capabilities but also the biocompatibility and especially the biofunctionality of materials. Here we show extensive biocompatibility studies of gallium nitride and, for the first time, a biofunctionality assay using ionizing radiation. Analytical sensor devices are used in medical settings, as well as for cell- and tissue engineering. Within these fields, semiconductor devices have increasingly been applied for online biosensing on a cellular and tissue level. Integration of advanced materials such as gallium nitride into these systems has the potential to increase the range of applicability for a multitude of test devices and greatly enhance sensitivity and functionality. However, for such applications it is necessary to optimize cell-surface interactions and to verify the biocompatibility of the semiconductor. In this work, we present studies of mouse fibroblast cell activity grown on gallium nitride surfaces after applying external noxa. Cell-semiconductor hybrids were irradiated with X-rays at air kerma doses up to 250 mGy and the DNA repair dynamics, cell proliferation, and cell growth dynamics of adherent cells were compared to control samples. The impact of ionizing radiation on DNA, along with the associated cellular repair mechanisms, is well characterized and serves as a reference tool for evaluation of substrate effects. The results indicate that gallium nitride does not require specific surface treatments to ensure biocompatibility and suggest that cell signaling is not affected by micro-environmental alterations arising from gallium nitride-cell interactions. The observation that gallium nitride provides no bio-functional influence on the cellular environment confirms that this material is well suited for future biosensing applications without the need for additional chemical surface modification.

Boosting oncolytic adenovirus potency with magnetic nanoparticles and magnetic force.

Oncolytic adenoviruses rank among the most promising innovative agents in cancer therapy. We examined the potential of boosting the efficacy of the oncolytic adenovirus dl520 by associating it with magnetic nanoparticles and magnetic-field-guided infection in multidrug-resistant (MDR) cancer cells in vitro and upon intratumoral injection in vivo. The virus was complexed by self-assembly with core-shell nanoparticles having a magnetite core of about 10 nm and stabilized by a shell containing 68 mass % lithium 3-[2-(perfluoroalkyl)ethylthio]propionate) and 32 mass % 25 kDa branched polyethylenimine. Optimized virus binding, sufficiently stable in 50% fetal calf serum, was found at nanoparticle-to-virus ratios of 5 fg of Fe per physical virus particle (VP) and above. As estimated from magnetophoretic mobility measurements, 3,600 to 4,500 magnetite nanocrystallites were associated per virus particle. Ultrastructural analysis by electron and atomic force microscopy showed structurally intact viruses surrounded by magnetic particles that occasionally bridged several virus particles. Viral uptake into cells at a given virus dose was enhanced 10-fold compared to nonmagnetic virus when infections were carried out under the influence of a magnetic field. Increased virus internalization resulted in a 10-fold enhancement of the oncolytic potency in terms of the dose required for killing 50% of the target cells (IC(50) value) and an enhancement of 4 orders of magnitude in virus progeny formation at equal input virus doses compared to nonmagnetic viruses. Furthermore, the full oncolytic effect developed within two days postinfection compared with six days in a nonmagnetic virus as a reference. Plotting target cell viability versus internalized virus particles for magnetic and nonmagnetic virus showed that the inherent oncolytic productivity of the virus remained unchanged upon association with magnetic nanoparticles. Hence, we conclude that the mechanism of boosting the oncolytic effect by magnetic force is mainly due to the improved internalization of magnetic virus complexes resulting in potentiated virus progeny formation. Upon intratumoral injection and application of a gradient magnetic field in a murine xenograft model, magnetic virus complexes exhibited a stronger oncolytic effect than adenovirus alone. We propose that this approach would be useful during in vivo administration to tumor-feeding blood vessels to boost the efficacy of the primary infection cycle within the tumor. For systemic application, further modification of magnetic adenovirus complexes for shielding and retargeting of the whole magnetic virus complex entity is needed.