Imaging and therapy of brain cancer using theranostic nanoparticles

Résumé

Glioma is a general term used to describe the primary brain tumors that are the most common in the central nervous system (CNS). Glioblastoma multiforme (GBM) is the most malignant type which constitutes more than 60% of all brain tumors in adults. Despite the variety of therapies researched against GBM, it is still a deadly disease with extremely poor prognosis (average survival of 18 months). One of the main strategies to achieve lower mortality is the early detection, localization and typing, followed the precise therapy and monitoring of the tumor. In the field of diagnosis, nanotechnology plays an important role and several nanosystems have improved the accuracy of different imaging techniques. This is the case of superparamagnetic iron oxide nanoparticles (SPION) for magnetic resonance imaging (MRI) or gold nanoparticles (AuNP) for computed tomography (CT). From the therapeutic point of view, doxorubicin (DOX) is a potent antineoplastic drug widely used in the treatment of cancer. Administered in a free form it does not target the tumor and high doses are needed, which cause cardiotoxicity. Nanomedicine is also considered an interesting alternative since the drug encapsulated has greater the bioavailability, decreasing the toxicity and increasing the efficacy of the treatment. On top of that, numerous studies such as those carried out by our research group have shown that by modifying the surface of the nanocarriers with for example the surfactant Tween® 80 (T80), they are able to cross the blood brain barrier (BBB): failure to do so is the main cause of chemotherapy failure in CNS diseases. It is indeed well acknowledged that magnetic nanoparticles, like the SPION already mentioned, could also improve the specificity of treatment since they can be attracted by magnets. All in all, it is possible to combine the application of nanotechnology to the diagnosis and treatment of diseases such as glioma, leading to theragnosis. As a matter of fact, diagnostic/therapeutic nanoplatforms are a new and promising step towards personalized medicine and early diagnosis. The primary hypothesis of this project is that the coencapsulation of DOX (as a treatment agent) and AuNP or SPION (as a diagnostic agents) in the same nanosystem will allow NP monitoring and, therefore, tumor monitoring. Apart from that, the encapsulation of DOX in polymeric nanoparticles (PNP) coated with different surfactants along with magnetic targeting of SPION will allow BBB permeation and therefore glioma therapy improvement. Overall, the main objective of this project is the design and development of nanosystems for the treatment and diagnosis of cancer. The second objective is to study the influence of different surfactants in the BBB permeation, as well as the influence of magnetic targeting of SPION inside the brain.