Enhancing Pt (IV) Complexes Anticancer Activity Upon Encapsulation in Stimuli Responsive Nanocages.

Platinum-based chemotherapy is the first-line treatment for different cancer types and in particular for malignant pleural mesothelioma patients (a tumor histotype with urgent medical needs). Herein we present a strategy to stabilize, transport and intracellular release of a platinum IV (Pt IV ) prodrug using a breakable nanocarrier. Its reduction, and therefore activation as anticancer drug, is promoted by the presence of glutathione in neoplastic cells that also causes the destruction of the carrier. The nanocage presents a single internal cavity in which the hydrophobic complex (Pt(dach)Cl 2 (OH) 2 ), (dach = R,R-diaminocyclohexane) has been encapsulated. We have evaluated the in vitro uptake and the internalization kinetics in cancer model cells and using flow cytometry analysis, demonstrated the successful release and activation of the Pt based drug inside cancer cells. The in vitro findings were confirmed by the in vivo experiments on a mice model obtained by xenografting MPM487, a patient-derived malignant pleural mesothelioma. MPM487 confirmed the well-known resistance of malignant pleural mesothelioma to cisplatin treatment while an interesting 50% reduction of tumor growth was observed when mice were treated with the Pt IV , entrapped in the nanocages, at an equivalent dose of platinum complex. This article is protected by copyright. All rights reserved.