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BP: Fachverband Biologische Physik
BP 5: Focus Session NanoAgents
BP 5.5: Talk
Monday, March 27, 2023, 16:30–16:45, TOE 317
DNA origami agents for the efficient treatment of solid tumors — •Johann Moritz Weck1, Merve-Zeynep Kesici1, Cornelia Monzel2, and Amelie Heuer-Jungemann1 — 1Max Planck Institut für Biochemie, Am Klopferspitz 18, 82152 Martinsried — 2Heinrich Heine Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf
We previously used DNA origami as a platform to pre-cluster Fas ligands (FasL) of the tumor necrosis factor receptor superfamily (TNFRSF) with nanometer precision in varying patterns and presented those to HeLa cells in a 2D cell culture model. We found up to a 100x increase of potency upon pre-clustering FasL in hexagonal geometries, a high sensitivity towards inter-ligand distance and a dependency on linker rigidity. In order to use this knowledge for the advancement of TNRSF ligand-based therapeutics, we investigated the interactions of DNA origami nanoagents with solid tumors. Certain aspects of cancer cell biology, such as the complex biological environment of solid tumors cannot be efficiently simulated in regular 2D cell culture systems. Using a 3D tumor spheroid model, we here show that FasL-DNA origami nanoagents are able to strongly affect the growth of 3D tumor spheroids. Partial dissolution of 3D tumoroids is observed after exposure to the nanoagents. We provide insights into DNA origami tumor spheroid penetration ability as well as a threshold like behavior of signaling initiation, and design rules for nanomaterial based therapeutics.