The mesenchymal stromal cells increased the activity on glioblastoma of a new delivered anticancer platinum-drug

Objective: Glioblastoma multiforme (GBM) is nowadays the most aggressive tumor affecting brain in adults with a very poor prognosis due to limited therapies and systemic cytotoxicity. Among the different new drugs, recently has been reported the in vitro anti-glioma activity of a new cationic platinum(II) complex bearing 8-aminoquinoline as chelating ligand (Pt-8AQ The purpose of this research was to confirm the activity of Pt-8AQ on U87-GM spheroid and to investigate the ability of Mesenchymal Stromal Cells (MSCs) to incorporate and release Pt-8AQ in active form. Materials and methods: Dosages of 20 µM were employed for the inhibition of the spheroid formation and 5 µM of the drug, added to pre-formed spheroids, produced a significant dramatic degradation after 96 h of treatment. The MSCs were primed with Pt-8AQ in optimized conditions and the secretome was analyzed for the activity of Pt-8AQ and the presence of Evs. Results: We confirm our previous results in traditional 2D cell culture by demonstrating the anticancer activity of Pt-8AQ against U87-GM cells grown as 3D multicellular spheroids. The principal results showed that Pt-8AQ incorporated by MSCs was released in the secretome and exerted a significant anticancer higher in comparison to free drug’s one. The release of Pt-8AQ did not occur in Evs, as found with other drugs, but could be delivered bound to some particular carrier able to enhance its bioavailability and efficacy. Some hypotheses are discussed to explain this surprisingly finding that however will need more investigations. Conclusions: The major conclusions are that cell mediated drug delivery systems could provide a potential approach to facilitate the GMB therapy by intra-tumoral administration of cells loaded with Pt-8AQ being MSCs able to integrate into the tumor mass and exert high therapeutic efficacy in situ. The increased efficacy of Pt-8AQ delivered by MSCs even suggests to deeper investigate a possible direct use of MSCs secretome both in situ and/or by systemic administration being secretome able to pass the blood-brain tumor. (P - 17)