Abstract
Electrodynamic therapy (EDT) has recently emerged as a potential external field responsive approach for tumor treatment. While it presents a number of clear superiorities, EDT inherits the intrinsic challenges of current reactive oxygen species (ROS) based therapeutic treatments owing to the complex tumor microenvironment, including glutathione (GSH) overexpression, acidity and others. Herein for the first time, iron oxide nanoparticles are decorated using platinum nanocrystals (Fe3O4@Pt NPs) to integrate the current EDT with chemodynamic phenomenon and GSH depletion. Fe3O4@Pt NPs can effectively induce ROS generation based on the catalytic reaction on the surface of Pt nanoparticles triggered by electric field (E), and meanwhile it may catalyze intracellular H2O2 into ROS via Fenton reaction. In addition, Fe3+ ions released from Fe3O4@Pt NPs under the acidic condition in tumor cells consume GSH in a rapid fashion, inhibiting ROS clearance to enhance its antitumor efficacy. As a result, considerable in vitro and in vivo tumor inhibition phenomena are observed. This study has demonstrated an alternative concept of combinational therapeutic modality with superior efficacy.
Highlights
Reactive oxygen species (ROS), containing hydroxyl radical (·OH), superoxide (O2·−), singlet oxygen (1O2) and hydrogen peroxide (H2O2), widely exist in living organisms [1,2,3]
Synthesis of Fe3O4@platinum nanoparticles (Pt NPs) Fe3O4 NPs were synthesized and modified with amino groups before the in situ growth of Pt NPs on the surface. Fe3O4@Pt NPs were modified with polyethylene glycol (PEG) to enhance its stability (Fig. 2a)
As shown in the TEM images, Pt nanocrystals are anchored at the Fenton activity and electrodynamic properties In order to avoid the uncertainty in ROS evaluation induced by oxygen generated from Pt nanocrystals, the ·OH production of Fe3O4 NPs was examined to reveal the Fenton activity of Fe3O4@Pt NPs using 3,3′,5,5′-tetramethylbenzidine (TMB)
Summary
Reactive oxygen species (ROS), containing hydroxyl radical (·OH), superoxide (O2·−), singlet oxygen (1O2) and hydrogen peroxide (H2O2), widely exist in living organisms [1,2,3]. It plays a crucial role in physiological functions, which can modulate proteins, produce hormones, regulate cell signaling, mediate inflammation, and eliminate pathogens. Glutathione peroxidase (GSH-Px) are able to catalyze the reduction of H 2O2 with GSH as reductant [27] In this process, GSH can be consumed and converted into GSSG by the oxidation of H2O2 [28], favoring current ROS-based therapies
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