Project 457631

Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumour, with patients having a median survival rate of fewer than 15 months. Moreover, the first-line approved therapy, drug temozolomide plus radiotherapy, failed to increase overall survival substantially. GBM is protected by the natural blood-brain barrier, which hampers the penetration of conventional chemotherapeutics. Furthermore, within the smaller arsenal of drugs left, the candidate needs to elicit strong anti-cancer activity with moderate side effects on the healthy neuronal cells. It is safe to say that the challenges imposed by GBM contribute to the lack of a current effective therapeutic intervention for this type of cancer. For these reasons, efforts are currently being devoted to finding new GBM targeted approaches. Here, we propose to use microRNAs as a novel strategy against the disease. MicroRNAs are gaining importance as an anti-cancer therapy as they can induce the degradation of proteins that mediate cancer progression and drug resistance. However, microRNAs are classified as genetic materials and need delivery agents to promote therapeutic efficiency. To overcome such barriers, we envision a hybrid lipid/polymer nanoparticle composed of biocompatible materials that can co-encapsulate microRNA and temozolomide. In addition, our system can recognize and target cancer cells, sparing the healthy nervous tissue from systemic toxicity. The targeted nanoparticles will deliver the payload predominantly to cancer cells, increasing the concentration of pharmacological agents at the right place to induce the therapeutic effect. Our goal is to engineer the nanoparticles, characterize the system and validate it in vitro and in vivo with regard to efficiency and biosafety of the nanoparticles. This project relies on a nanotechnology-targeted strategy that will provide valid scientific evidence to contribute to cancer research and open new directions in the treatment of GBM.