Friday, 19 November, 13:00
Novel polymers and polymeric nanoparticles for glioblastoma targeted drug delivery
Dr Grabrucker received his MSc in Biology with a focus on human and animal genetics in 2005 from the Technical University of Munich (TUM), Germany. From 2005 to 2009, he investigated the molecular mechanisms of synaptic plasticity in his doctoral work at Ulm University, Germany. After receiving his PhD in molecular medicine, he continued his neuroscientific research in the United States at Stanford University’s Department of Psychiatry and Behavioral Sciences until 2011. In 2011, he returned to the University of Ulm as Assistant Professor, where he headed the research group “Molecular analysis of synaptopathies”. At the same time, he took up the position of Executive Director of the Neurocenter of the University of Ulm. Since 2017, he has been at the University of Limerick (UL), where he is Senior Lecturer in the Department of Biological Sciences and Lead of the Bio Materials Research Cluster of the Bernal Institute of UL.
Dr Grabrucker’s primary research focus is in the area of translational neuroscience. He has secured more than 2.5 Mio EUR funding in the last years from national, industrial and private foundations sources. He represents Ireland in the members’ committee of EU funded COST research networks (i.e. COMULIS – correlated multimodal imaging) and serves as an expert reviewer for the Deutsche Forschungsgemeinschaft (DFG), Agence Nationale de la Recherche (ANR), Swiss National Science Foundation (SNF), National Science Center, Poland, and the European Commission, and is on the editorial board of several journals. Since his PhD in 2009, he has published over 70 articles in peer reviewed journals, including EMBO J, Nature, Brain, Science Transl. Medicine and Journal of Controlled Release, 14 book chapters, and 3 books.
Glioblastoma Multiforme (GBM), the most common adult malignant brain tumour, affects 5 in 100,000. Discovered in late-stage, the life expectancy is <15 months. Current treatments are highly aggressive and extend life by little more than a year. Only four anti-GBM chemotherapeutics are FDA approved due to toxic effects and lack of improved life expectancy. Most newly discovered drugs fail due to poor solubility, stability, bioavailability, blood-brain barrier (BBB) crossing, high first-pass clearance, and toxicity. Nanomedicines (NMeds) have distinct advantages such as increasing biodistribution, circulation, site accumulation, lowering toxicity and immune response. In this talk, Dr Grabrucker will summarise data and present unpublished new findings of projects in collaboration with the University of Modena and Reggio Emilia (UNMR).
Together, the partners designed a new ROS-responsive prodrug by using Melphalan (MPH) covalently coupled with methoxy polyethylene glycol (mPEG) through a ROS-cleavable group thioketal (TK), demonstrating the capacity to self-assemble into nanosized micelles. These nanocarriers showed no cytotoxicity of the prodrug on healthy cells (i.e. astrocytes), but anti-tumoral activity on GBM cells expressing high levels of ROS. Now, the surface of these nanocarriers has been modified to allow BBB crossing and GBM cell targeting.
Hopefully, these improved NMeds will advance drug delivery research in GBM due to their ability to transport drugs safely/efficiently to targeted organs and release them in a controlled manner.