Nanomedicine for glioblastoma therapy
The main objective of this project is to establish a new therapeutic approach for cancer treatment in general and for glioblastoma (GBM) in particular, a tumor for which there is no effective treatment. Novelty of the project relies not only on the use of RNAi technology (more specifically siRNA) to knock down selected proteins involved in tumoral cell survival and proliferation making them more susceptible to anticancer drugs and/or radiation but also on the use of novel cuttingedge multitasking nanoparticles (NPs). The specific siRNAs will be target-delivered by these NPs that will be fine-tuned in their structure and chemical surface to perform efficiently the tasks required for targeting an intracerebral glioblastoma xenograft: blood brain barrier crossing, siRNA target-delivered or tumor imaging. There are several relevant issues that are addressed by the project:
a) Improving BBB crossing by NPs;
b) toxicity of the NPs in vivo and in vitro (on healthy and tumoral cells);
c) fine tuning of the 3D structure of the NPs based on feed-back from biological experiments
d) the use of selected fresh xenografted human tumors obtained from cells isolated from patients to increase the likeliness that the response of the mice to the nanoplexes could enhance our understanding of key aspects of glioblastoma biology and, in proper time, reach the clinical setting.
The project will use a multidisciplinary approach strategy and all the techniques that are going to be used in the project are commonly used in the laboratories of the members of the consortium which decreases the technological risk of the project. The final result of the development of the project will be to provide the “proof-of-concept” in an animal model of xenografted human glioblastoma cells, obtained from patients by the clinicians participating in the consortium, that RNAi therapeutics is effective in cancer treatment either by itself or by potentiating the effect of anticancer drugs.