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 platinumIV (PtIV) 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)Cl2(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 PtIV, entrapped in the nanocages, at an equivalent dose of platinum complex.

Enhancing Pt (IV) Complexes Anticancer Activity Upon Encapsulation in Stimuli Responsive Nanocages / M. Sancho-Albero, G. Facchetti, N. Panini, M. Meroni, E. Bello, I. Rimoldi, M. Zucchetti, R. Frapolli, L. De Cola. - In: ADVANCED HEALTHCARE MATERIALS. - ISSN 2192-2659. - 12:17(2023 Jul 06), pp. e2202932.1-e2202932.25. [10.1002/adhm.202202932]

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

G. Facchetti
Secondo
;
I. Rimoldi;L. De Cola
Ultimo
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 we present a strategy to stabilize, transport and intracellular release of a platinumIV (PtIV) 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)Cl2(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 PtIV, entrapped in the nanocages, at an equivalent dose of platinum complex.
Organosilica; mesothelioma; nanocages; platinum complexes; tumor reduction;
Settore CHIM/03 - Chimica Generale e Inorganica
Settore CHIM/06 - Chimica Organica
   A KEY TO THE RATIONAL DESIGN OF EXTRACELLULAR VESICLES-MIMICKING NANOPARTICLES
   MIMIC-KeY
   European Commission
   Horizon 2020 Framework Programme
   964386
6-lug-2023
12-mar-2023
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/961280
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