Oxygen-supplied electrotherapy for enhanced photodynamic synergistic therapy overcomes hypoxia tumor microenvironment

Photodynamic therapy (PDT) has lately been identified as a promising anticancer method and gained tremendous interest due to its controllability, non-invasive nature, and negligible side effects. Nevertheless, the development of PDT is hampered by two factors. One is the insufficient tissue penetration of phototherapy laser, resulting in restricted treatment sites. Another one is the substantial dependence of reactive oxygen species (ROS) formation on oxygen concentration. Therefore, a strategy to promote ROS generation by overcoming the hypoxia microenvironment is critical to cancer therapy. Electrolysis of water is known to be a rapid and relatively secure method for producing oxygen. Thus, in this study, electrotherapy was introduced to alleviate the tumor hypoxia by producing oxygen in situ, hence boosting the PDT efficacy, namely E-PDT. Black phosphorus (BP) based nanomaterials were selected as clearable photosensitizers with outstanding PDT performance. Experiments conducted both in vitro and in vivo indicated that E-PDT performed superior therapeutic effects with the in situ generation of oxygen by electrotherapy compared with other groups. This work suggests a promising strategy for phototherapeutic anticancer efficiency enhancement.