Iron-based MOF with Catalase-like activity improves the synergistic therapeutic effect of PDT/ferroptosis/starvation therapy by reversing the tumor hypoxic microenvironment.

Abstract

Reversing the hypoxic microenvironment of tumors is an important method to enhance the synergistic effect of tumor treatment. In this work, we developed the nanoparticles called Ce6@HGMOF, which consists of a photosensitizer (Ce6), glucose oxidase (GOX), chemotherapy drugs (HCPT) and an iron-based metal-organic framework (MOF). Ce6@HGMOF can consume glucose in tumor cells through "starvation therapy", cut off their nutrition source, and produce gluconic acid and hydrogen peroxide (H₂O₂). Utilizing this feature, Ce6@HGMOF can produce oxygen through catalase-like catalytic activity, thereby reversing the hypoxic microenvironment of tumors. This strategy of changing the hypoxic environment can help to slow down the growth of tumor blood vessels and improve the drug-resistant microenvironment to some extent. Meanwhile, increasing the supply of oxygen can enhance the effect of photodynamic therapy (PDT) and enhance the oxidative stress damage caused by reactive oxygen species (ROS) in tumor cells. On the other hand, cancer cells usually produce higher levels of glutathione (GSH) to adapt to high oxidative stress and protect themselves. The Ce6@HGMOF we designed can also consume GSH and induce ferroptosis of tumor cells through Fenton reaction with H₂O₂, while enhancing the effect of PDT. This innovative synergistic strategy, the combination of PDT/ferroptosis /starvation therapy, can complement each other and enhance each other. It has great potential as a powerful new anti-tumor paradigm in the future.