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.

Sancho‐albero, M., Facchetti, G., Panini, N., Meroni, M., Bello, E., Rimoldi, I., et al. (2023). Enhancing Pt(IV) Complexes' Anticancer Activity upon Encapsulation in Stimuli‐Responsive Nanocages. ADVANCED HEALTHCARE MATERIALS, 12(17 (July 6, 2023)) [10.1002/adhm.202202932].

Enhancing Pt(IV) Complexes' Anticancer Activity upon Encapsulation in Stimuli‐Responsive Nanocages

Meroni, Marina;
2023

Abstract

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.
Articolo in rivista - Articolo scientifico
mesothelioma; nanocages; organosilica; platinum complexes; tumor reduction;
English
12-mar-2023
2023
12
17 (July 6, 2023)
2202932
open
Sancho‐albero, M., Facchetti, G., Panini, N., Meroni, M., Bello, E., Rimoldi, I., et al. (2023). Enhancing Pt(IV) Complexes' Anticancer Activity upon Encapsulation in Stimuli‐Responsive Nanocages. ADVANCED HEALTHCARE MATERIALS, 12(17 (July 6, 2023)) [10.1002/adhm.202202932].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/457259
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