Light-Regulated NO Release as a Novel Strategy To Overcome Doxorubicin Multidrug Resistance.
Nitric oxide (NO) release from a suitable NO photodonor (NOP) can be fine-tuned by visible light stimuli at doses that are not toxic to cells but that inhibit several efflux pumps; these are mainly responsible for the multidrug resistance of the anticancer agent doxorubicin (DOX). The strategy may thus increaseDOXtoxicity against resistant cancer cells. Moreover, a novel molecular hybrid covalently joiningDOXandNOPshowed similar increased toxicity toward resistant cancer cells and, in addition, lower cardiotoxicity thanDOX. This opens new and underexplored approaches to overcoming the main therapeutic drawbacks of this chemotherapeutic based on light-controlled release of NO.
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Konstantin
K
Chegaev
Laboratory of Photochemistry, Department of Drug Sciences, University of Catania , I-95125 Catania, Italy.
Aurore
A
Fraix
Department of Oncology, University of Torino , Via Santena 5/bis, I-10126 Torino, Italy.
Elena
E
Gazzano
Department of Oncology, University of Torino , Via Santena 5/bis, I-10126 Torino, Italy.
Gamal Eldein F
GE
Abd-Ellatef
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Marco
M
Blangetti
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Barbara
B
Rolando
STMicroelectronics , Stradale Primosole 50, I-95121 Catania, Italy.
Sabrina
S
Conoci
Department of Oncology, University of Torino , Via Santena 5/bis, I-10126 Torino, Italy.
Chiara
C
Riganti
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Roberta
R
Fruttero
Department of Drug Science and Technology, University of Torino , I-10125 Torino, Italy.
Alberto
A
Gasco
Laboratory of Photochemistry, Department of Drug Sciences, University of Catania , I-95125 Catania, Italy.
Salvatore
S
Sortino
Nitric oxide; doxorubicin; efflux pump inhibition; light; multidrug resistance