Targeted delivery of theragnostic nanoparticles in glioblastoma

As a promising approach to cure or to image cancer tumors or metastasis, nanoparticles can play an important role for the future theragnostic medicine, in drug delivery and/or as a new contrast agent for in vivo imaging. The mesoporous silica nanoparticles (MSNP) have the unique ability to encapsulate a large panel of molecule allowing combined therapeutic drugs to be loaded. While many drugs do not reach therapeutic levels in the tumor tissue, lipid bilayer surrounded MSNP (protocells) have emerged with enhanced targeted efficiency to kill cancer cells. The TheraG project aims at phasing in cancer cell targeting and therapeutic properties of new generation of protocells (CRP-Gabriel Lippmann property). The Glioblastoma (GBM) is characterized by high heterogeneity at the cellular and molecular level that can be explained by the presence of Glioblastoma cancer stem cells capable of differentiation into the actively expanding tumor bulk. Then, active targeting to extracellular proteins overexpressed in the different subpopulation of brain cancer cells will be addressed using an association of specific antibodies, currently in use in clinic, to the vehicle. In accordance with their overexpressions on the different GBM subpopulations, we intend to target the Epidermal Growth Factor Receptor (EGFR) and its most common variant EGFRvIII and, the extracellular matrix glycoprotein Tenascin-C upregulated in the undifferentiated Glioblastoma stem cell. A drug combination of the alkylating agent Temozolomide and the differentiating drug Doxorubicin will be encapsulated to eradicate the GBM subpopulations.