Abstract
The induction of oxidative species, driven by oscillating electric field (E), has recently emerged as an effective approach for tumor inhibition, so-called electrodynamic therapy (EDT). While it offers a series of advantages attracting considerable attention, the fundamental mechanism and improvement strategies for EDT approach are being endeavored extensively with the aid of new material explorations. An interesting phenomenon observed in early studies is that the on-site concentration of chloride ion is highly favored for the induction of oxidative species and the efficacy of tumor inhibition. Following this discovery ignored previously, here for the first time, fine Pt/Cu alloy nanoparticles (PtCu3 NPs) are integrated with chloride ion transporter (CIT) for EDT-based combinational therapy. In this system, while PtCu3 NPs induce oxidative species under an electric field, it also effectively transforms endogenous H2O2 into •OH and consumes intracellular glutathione (GSH). More importantly, with the aid of CIT, PtCu3-PEG@CIT NPs promote the intracellular concentration of chloride ion (Cl-) by transporting extracellular Cl-, facilitating the generation of oxidative species considerably. Meanwhile, CIT delivered intracellularly increases lysosomal pH, leading to the disruption of cellular autophagy and weakening the treatment resistance. In consequence, significant tumor inhibition is enabled both in vitro and in vivo, due to the combination of unique characteristics offered by PtCu3-PEG@CIT.