Near infrared triggered cascade reactions for photothermal/chemodynamic synergistic therapy

Abstract

In recent years, solving the problem of insufficient H₂O₂ levels at tumor sites has become the key for chemodynamic therapy (CDT). GOx is an efficient H₂O₂ producing enzyme, but the anoxic environment of the tumor cannot meet its continuous oxygen consumption, thus limiting the H₂O₂ production. In this work, perfluoropentane (PFP) was used as an oxygen carrier to deliver oxygen to the tumor site for an intelligent photothermal release, thus achieving photolock-free H₂O₂ generation. First, mesoporous copper sulfide nanoparticles (denoted as HMC) were prepared, surface-modified with GOx (denoted as HMCG), and then loaded with PFP and oxygen (PO@HMCG) to achieve photolocation-induced photothermal and chemokinetic treatment. Among these, HMC has photothermal conversion performance. Under near infrared light, it releases Cu²⁺/Cu⁺, realizing photothermal enhancement of ROS generation and GSH consumption, thus enhancing intracellular oxidative stress. At the same time, when the local temperature rises above the boiling point of PFP, the transformation of PFP from liquid to gaseous state is realized and oxygen is released to provide raw material for the catalytic process of GOx and activate the synthesis of H₂O₂. In vitro and in vivo experiments have shown that PO@HMCG can achieve a combination of the photothermal and chemodynamic treatment of photo-unlocking not only realizing an excellent tumor inhibition effect but also avoid damage to the normal tissue.