Redox Mediator-Assisted Iron-Based Nanoparticles for pH-Independent Photothermal-Chemodynamic Tumor Therapy

Utilizing the Fenton reaction to convert hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH), chemodynamic therapy (CDT) based on iron-based nanoparticles (NPs) has been investigated widely. However, several problems, e.g., Fenton activity acidity dependence, inert ferric hydroxide (Fe(OH)x) precipitation in the tumor microenvironment, and sluggish conversion between ferric and ferrous ions, further eliminate the enhancement of CDT efficiency based on iron-based NPs. Herein, a polyethylene glycol (PEG)-modified chelating complex ferric-polydopamine (Fe-PDA-PEG) NP is structured to serve as an agent for pH-independent photothermally enhanced CDT, which overcomes the above issues simultaneously. Benefiting from PDA (a kind of redox mediator) with high electron transfer rates and strong chelation, iron ions within Fe-PDA-PEG NPs can achieve the Fe3+/Fe2+ cycle readily, resulting in high efficiency of •OH generation even at the neutral pH. In addition, the noteworthy photothermal performance of Fe-PDA-PEG NPs can obtain superior photothermal therapy (PTT) and enhance the effect of CDT simultaneously. After combining with PTT and CDT, excellent antitumor effects in vitro and in vivo are obtained. This study is an emerging direction for nanotherapeutic agents to improve the antitumor activity by the introduction of redox mediators with high electron transfer rates and excellent photothermal performance to achieve pH-independent photothermally enhanced CDT.