DNA-based Self-Assembly of Chiral Plasmonic Nanostructures with Tailored Optical Response

Surface plasmon resonances generated in metallic nanostructures can be utilized to tailor electromagnetic fields. The precise spatial arrangement of such structures can result in surprising optical properties that are not found in any naturally occurring material. Here, the designed activity emerges from collective effects of singular components equipped with limited individual functionality. Top-down fabrication of plasmonic materials with a predesigned optical response in the visible range by conventional lithographic methods has remained challenging due to their limited resolution, the complexity of scaling, and the difficulty to extend these techniques to three-dimensional architectures. Molecular self-assembly provides an alternative route to create such materials which is not bound by the above limitations. We demonstrate how the DNA origami method can be used to produce plasmonic materials with a tailored optical response at visible wavelengths. Harnessing the assembly power of 3D DNA origami, we arranged metal nanoparticles with a spatial accuracy of 2 nm into nanoscale helices. The helical structures assemble in solution in a massively parallel fashion and with near quantitative yields. As a designed optical response, we generated giant circular dichroism and optical rotary dispersion in the visible range that originates from the collective plasmon-plasmon interactions within the nanohelices. We also show that the optical response can be tuned through the visible spectrum by changing the composition of the metal nanoparticles. The observed effects are independent of the direction of the incident light and can be switched by design between left- and right-handed orientation. Our work demonstrates the production of complex bulk materials from precisely designed nanoscopic assemblies and highlights the potential of DNA self-assembly for the fabrication of plasmonic nanostructures.Comment: 5 pages, 4 figure

Retargeted adenoviruses for radiation-guided gene delivery

The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment

Benefits and risks of psychiatric actions and the patientʼs right of self-determination

The history of psychiatry shows that a right of self-determination of the mentally ill was widely unknown in the nineteenth century and became known in medicine through the juridical concept of informed consent as late as in the second half of the twentieth century. Since the beginning of the twenty-first century this human right has been increasingly recognized and respected in medical practice. This change of recognition is contributing to a change from a paternalistic to a participative medical attitude. In the context of an emancipatory development of society the increasing possibilities of effective therapies, which are rarely without risks, stimulate the necessity to inform the patient about the intended benefits and the potential risks of the recommended intervention. This gives the patient the opportunity to exercise the right of self-determination. Furthermore, by the transition from very successful acute medicine, although often with only short-term contact between physician and patient to long-term therapies of chronic diseases, the possibilities to understand the patient are increased, particularly in the mentally ill patient. This also enables the individual characteristics to be recognized better, both the restrictions and capabilities, to experience the patient as an individual, as a human being with individual peculiarities and to respect the right of self-determination by helping the patient to understand the benefits and risks of a recommended intervention and to balance them in a self-determined mode.Die Geschichte der Psychiatrie zeigt, dass ein Selbstbestimmungsrecht des psychisch Kranken im 19. Jahrhundert weitgehend unbekannt war, erst spät in der 2. Hälfte des 20. Jahrhunderts mit dem rechtlichen Konzept der Einwilligung nach Aufklärung, dem „informed consent“, in der Medizin bekannt wurde und seit Beginn des 21. Jahrhunderts in der medizinischen Praxis zunehmend wahrgenommen und respektiert wird; diese Wahrnehmungsänderung trägt zu einem Wandel von einer paternalistischen zu einer partizipativen ärztlichen Einstellung bei. Im Kontext einer emanzipatorischen Entwicklung der Gesellschaft nimmt mit den wachsenden Möglichkeiten wirksamer Therapien, die selten ohne Risiken sind, die Notwendigkeit zu, den Patienten über den intendierten Nutzen und potenzielle Risiken der empfohlenen Intervention zu informieren und ihm damit die Voraussetzung zu schaffen, sein Selbstbestimmungsrecht wahrzunehmen. Zudem wachsen mit dem Übergang von einer sehr erfolgreichen Akutmedizin mit allerdings oft nur kurzem Arzt-Patienten-Kontakt zur Langzeitmedizin chronischer Erkrankungen die Möglichkeiten, den Patienten, insbesondere den psychisch Kranken, seine individuellen Eigenheiten, seine Einschränkungen und Fähigkeiten besser wahrzunehmen, ihn als Individuum, als Menschen in seiner jeweiligen Eigenart zu erleben und sein Selbstbestimmungsrecht zu respektieren, indem wir ihm dabei helfen, Nutzen und Risiken einer empfohlenen Intervention zu verstehen und selbstbestimmt abzuwägen