Journal
ADVANCED HEALTHCARE MATERIALS
Volume 12, Issue 17, Pages -Publisher
WILEY
DOI: 10.1002/adhm.202202932
Keywords
mesothelioma; nanocages; organosilica; platinum complexes; tumor reduction
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Platinum-based chemotherapy is the standard first-line treatment for various types of cancer, including malignant pleural mesothelioma. This study presents a strategy using a breakable nanocarrier to stabilize, transport, and release a platinum(IV) prodrug, which is activated by the presence of glutathione in neoplastic cells. In vitro and in vivo experiments demonstrate the successful release and activation of the Pt-based drug inside cancer cells, leading to a significant reduction in tumor growth.
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, a strategy is presented to stabilize, transport, and intracellularly release a platinum(IV) (Pt-IV) prodrug using a breakable nanocarrier. Its reduction, and therefore activation as an 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) is encapsulated. The in vitro uptake and the internalization kinetics in cancer model cells are evaluated and, using flow cytometry analysis, the successful release and activation of the Pt-based drug inside cancer cells are demonstrated. The in vitro findings are confirmed by the in vivo experiments on a mice model obtained by xenografting MPM487, a patient-derived malignant pleural mesothelioma. MPM487 confirms the well-known resistance of malignant pleural mesothelioma to cisplatin treatment while an interesting 50% reduction of tumor growth is observed when mice are treated with the Pt-IV, entrapped in the nanocages, at an equivalent dose of the platinum complex.
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