Conjugated Polymer Nanoparticles: A Novel Strategy to Combat Glioblastoma Multiforme

The most aggressive type of brain tumour is Glioblastoma multiforme (GBM). GBM encompasses 17% of all brain tumours, and the median survival for patients does not exceed 15 months. The diffuse nature of the disease and the high level of heterogeneity leads to ineffective surgical resection and diminished success of established therapies. A novel therapeutic option includes utilizing nanoparticles. My project specifically focuses on the molecular properties of Conjugated Polymer Nanoparticles (CPNs), which are comprised of a Poly-Isoindigo polymer and a fluorescently labelled Hyaluronic Acid (HA) coating. I will first study the CPN concentration-dependent effects on glioma cells in vitro by studying the cell cycle phase accessibility, cell proliferation, death, and metabolic activity. I will investigate the selectivity of targeting CD44, a HA receptor, positive cells by CPNs, comparing CD44+ and CD44- cells, separated using Fluorescence-Activated Cell Sorting (FACS), or by using CD44 knockdown.Finally, the bioavailability of CPNs will be assessed using an in vivo Zebrafish system. I will first evaluate any potential toxicity of CPNs on the Zebrafish, and then I will determine the optimal concentration and timing of CPN treatments. I will then investigate the effects of CPNs on xenografted U251tumours in vivo. This project will enhance our understanding of the CPN-mediated effects not only on the GBM cells but also in an in vivo setting allowing for further development of this therapeutic approach to potentially improve clinical outcomes in patients with GBM