GLIOTARG · Hydrogel containing Metal-Organic Polyhedra as scaffold agents for in vivo local gas delivery in glioma cancer tumours

The National Brain Tumor Society of America stated that glioblastoma is one of the most complex, deadly, and treatment-resistant cancers with an average length of survival of 8 months. Surgery is the primary form of treatment, and some drugs are approved for treatment, however, none of these treatments have significantly extended patient lives beyond extra months. Recurrence following surgery is a major problem and is often the ultimate cause of death. Accordingly, our specific aim is to target glioma cells with gas- Metal-Organic Polyhedra (MOP) conjugates after/before surgery removal of the tumor in in vivo mice models of glioblastoma cancer. Therapeutic gases (i.e. CO and NO) will be absorbed in the MOP cavity, while the surface will be functionalized for tumor targeting. The system will be dispersed in a biodegradable hydrogel, that will assist in the progressive delivery into the tumor cells once it is injected into the brain. Hydrogel will be tested as a gas-MOP system dispersion medium and as a conjugated treatment including already-known chemotherapeutic drugs for glioma (i.e., Temozolomide, Carmustine or Bevacizumab). The ultimate goal of the project is to create a patch made of bioresorbable hydrogel containing drug and MOP-gas conjugates for local release in glioblastoma tumoral cells. This dual system will be specifically and locally delivered in tumor cells by functionalization of MOP linkers to target and attach to the tumor. To the best of our knowledge, this is the first time that (i) Metal-Organic Polyhedras (MOPs) are used in cancer therapy as carrier systems and (ii) a combined treatment gas/drug is applied for glioblastomas to eliminate or reduce the tumor before/after surgery removal. This proposal achieves the aims of the European Research Area and is highly relevant to the Marie Curie Programme and to long-term career development.