Paving the way to the early diagnosis of glioblastoma

Nanobrain is part of the flagship project NanoMax and originates from the collaboration between four CNR Institutes: Nanoscienze (Nano), Neuroscienze (IN), Officina dei Materiali (IOM) and Istituto Nazionale di Ottica (INO). This project promotes the collaboration between the neuroscience and the nanofabrication technologies present in CNR. At the basis of this project is the consideration that the brain is biochemically isolated from the body by the Blood Brain Barrier (BBB): because of this defense, the large majority of factors circulating in the blood stream are not capable of reaching any brain target. Conversely, factors released in the brain and that might serve as biomarker of an ongoing pathology, cannot reach the blood stream in meaningful amounts. This diffusive barrier strongly limits our capacity of performing a non invasive diagnostic of brain pathologies and of targeting therapeutic compounds to the brain. With this project we intend to overcome this barrier by using new tools offered by the nanotechnology paradigm, with the final goal of increasing the sensitivity of the available tools for the early detection of biomarkers in the blood stream and to deliver nanofabricated carriers into the brain.
As pathological model we have selected the glioblastoma: this is an extremely aggressive brain tumor with an invariably poor prognosis. The selected markers will be revealed by a sensor functionalized with ligands immobilized on its surface. The ligand binding will be converted in a macroscopic signal following two different approaches. In one case we will measure the change of the resonance frequency of a nano-cantiliver oscillating under the influence of an external electric field. The second approach measures the tiny change in refraction index of the surface upon ligand binding. By exploiting the generation and propagation of plasmons on a nano-structured surface, this technology should be capable of revealing the binding of a few thousands molecules.
In the second part of this project we will visualize the trafficking of nano-particles through the BBB and their diffusion within the brain parenchyma and in a mouse model of glioblastoma. We will exploit the bright and stable florescence of semiconductor particles (quantum dots) to label and follow each isolated particle by means of 2-photon imaging. In this model the tumor will be labeled by the expression of Green Fluorescent Protein and we will be able to study the proliferation and differentiation of the tumor, the formation of new blood vessels and the diffusion of tagged nanoparticles in the tumor.