Martin Kluenker

Intrinsic superoxide dismutase activity of MnO nanoparticles enhances the magnetic resonance imaging contrast

Superoxide radicals are associated with the development of many severe diseases, such as cancer. Under nonpathogenic conditions, the natural enzyme superoxide dismutase (SOD) regulates the intracellular superoxide concentrations, but nearly all tumor tissues show reduced SOD levels. Selective imaging in early progression stages remains a key requirement for efficient cancer diagnosis and treatment. Magnetic resonance imaging (MRI) as a noninvasive tool with high spatial resolution may offer advantages here, but MRI contrast agents exhibiting a redox-triggered change in the image contrast towards superoxide radicals have not been reported so far. Here we show that manganese oxide (MnO) nanoparticles (NPs) exhibit an intrinsic SOD-like activity, which is higher than that of the native Mn-dependent SOD. In addition, MnO NPs significantly enhance the MRI contrast when exposed to superoxide radicals, making them responsive MRI contrast agents for the treatment and imaging of cancer cells with reduced SOD levels.

Bio-nano: Theranostic at Cellular Level

Functionalized nanoparticles are important platforms for targeted drug delivery and multimodal imaging. Materials scientists provide tailor-made tools for medical research, diagnosis and treatment. These tools are rationally designed to have defined functions. Still, the value of these tools can only be determined by the users in medical sciences that develop assays for applying these tools. Until now, little is known about the impact of multifunctional particles that display intrinsic chemical and physical asymmetry which poses new challenges for cells associated with the amphiphilicity, dipole moments and chemical diversity/patchiness of the functionalized nanoparticles. Why is it important to study the impact of anisotropic multifunctional particles on biological cells extending the intricacy of the problem even further? Current nanotechnology projects that started during the past few years focus on the “supramolecular” weak binding of functionalized particles with the goal to form larger ensembles with new functionalities. Thus, one may anticipate new phenomena associated with the exposure of human tissue to the primary building blocks of these new materials. Despite the challenges that still have to be met, multifunctional nanoparticles provide fascinating opportunities for tailoring properties that are not possible with other types of therapeutics. As more clinical data become available, the nanoparticle strategy will improve to such an extent that more sophisticated tools actually reach the clinic. Results from current trials are fueling the enthusiasm of researchers.

Zinc overload mediated by zinc oxide nanoparticles as innovative anti-tumor agent

The predicted global cancer burden is expected to surpass 20 million new cancer cases by 2025. Despite recent advancement in tumor therapy, a successful cancer treatment remains challenging. The emerging field of nanotechnology offers great opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor cells via a yet unknown mechanism, most likely involving the generation of reactive oxygen species (ROS). These nanoparticles are a promising therapeutic opportunity as zinc is a nontoxic trace element and its application in medically-related products is considered to be safe. We could show that ZnO NP can exert cytotoxic effects on several human tumor cell lines. There can be found ZnO NP concentrations which selectively damage tumor cells while human fibroblasts do not sustain lasting damage. Cytotoxicity is attributable to the release of zinc ions from the nanoparticles outside the cells as well as to a direct cell-nanoparticle interaction. This involves uptake of the particles into the tumor cells. With a silica shell the cytotoxicity can be delayed which can help in the future for a safe transport in the blood stream. Cellular damage finally cumulates in apoptotic cell death via zinc overload within 48 h after treatment with ZnO NP. A therapeutical perspective could be the targeted accumulation of ZnO NP at the tumor side to induce local zinc overload that substantially damages the tumor cells with no or low side effects. We suggest further studies to explore the potential of ZnO NP as an innovative anti-tumor agent.