GRK 2375:  Tumor-Targeted Drug Delivery

• Subject Area: Medicine
• Term: since 2018
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 331065168

The RTG Tumor-Targeted Drug Delivery generates basic knowledge and translational strategies to improve the treatment of cancer patients with drug delivery systems (DDS)-based therapies. As a joint effort between biologists, chemists, pharmacists, and clinicians, we perform research on targeted therapeutic and theranostic scenarios with a clear perspective for clinical translation and improved patient outcomes. This is achieved by centering our efforts on concrete medical needs and realistic clinical applications. The field of tumor-targeted drug delivery is dynamic and promising directions have been emerging, which will be integrated in the 2nd funding phase of our RTG: First, there are multiple rationales and opportunities for using DDS and nanomedicine formulations to boost the efficacy of cancer immunotherapy. These include the induction of immunogenic cell death, targeting of primary and secondary lymphoid organs, and delivery of immunomodulatory compounds to polarize the tumor microenvironment towards an immunotherapy-responsive phenotype. Second, mRNA and siRNA are attractive tools for cancer therapy. The in vivo delivery of mRNA and siRNA to tumors is challenging and requires new DDS designs and delivery concepts. These can include (bio)hybrid carrier materials composed by lipids, polymers or antibodies, and microbubble-based formulations for local ultrasound-triggered cargo release and cellular transfection. Third, artificial intelligence is promising for cancer diagnosis and precision therapy. Machine learning tools are also valuable for drug delivery research, contributing e.g., to formulation optimization, patient selection, therapy response prediction, therapy monitoring, and individualized adaption of treatments. Being in an environment with excellent computer scientists, we already started exploring advanced computational tools for several relevant purposes, including simulation of DDS self-assembly in microfluidics, early tumor detection and characterization, and prediction of nanomedicine tumor accumulation via biopsy biomarkers. Fourth, advanced in vitro test platforms are attracting more attention. In projects flanking our RTG, expertise has been built up in generating representative 3D tumor spheroid systems and in vitro test platforms. Techniques have been established for 3D bioprinting of vascularized tumors in which organoids can be implemented. These platforms will help bridging in vitro and in vivo studies and reduce the need for animal experiments according to the 3R principles. Thus, while preserving our overall goal to improve tumor targeted drug delivery in an interdisciplinary and integrative way, the 2nd funding phase will add most timely and promising new research areas to our RTG, thus, strongly promoting the trained doctoral researchers for their further careers and generating important knowledge for an improved cancer therapy.

• DFG Programme: Research Training Groups
• Applicant Institution: Rheinisch-Westfälische Technische Hochschule Aachen
• Participating Institution: DWI - Leibniz-Institut für Interaktive Materialien e.V.; an der RWTH Aachen; Fraunhofer-Institut für Molekularbiologie und Angewandte Oekologie
• Spokesperson: Professor Dr. Fabian Kiessling
• Participating Researchers: Privatdozent Dr.-Ing. Johannes Buyel; Professor Dr. Andreas Herrmann; Professorin Dr. Ruth Knüchel-Clarke; Professor Dr. Twan Lammers; Professorin Dr.-Ing. Laura De Laporte; Privatdozentin Dr. Wiltrud Lederle; Professor Dr. Christian Liedtke; Dr. Josbert Metselaar; Professor Dr. Felix Mottaghy; Privatdozentin Dr. Mirle Schemionek-Reinders; Professorin Dr. Rebekka Schneider-Kramann; Professor Dr. Christian Trautwein