Photodynamic Therapy Combined with Ferroptosis Is a Synergistic Antitumor Therapy Strategy

SIMPLE SUMMARY: In this work, we focused on the synergistic antitumor effects of photodynamic therapy and ferroptosis. First, we briefly introduced the basic theory of ferroptosis and photodynamic therapy. We explored the synergistic anti-tumor effect of photodynamic therapy combined with ferroptosis from a mechanism perspective. Secondly, we introduced the application of photodynamic therapy combined with ferroptosis, which mainly includes the construction of nanomaterials and drug combination. Nanomaterials can exert synergistic effects by activating anti-tumor immunity, improving the hypoxic microenvironment, and inhibiting tumor angiogenesis. The drug combination strategy has good application prospects and clinical significance.We also discussed the shortcomings of existing combination treatment strategies and potential solutions. In conclusion, photodynamic therapy combined with ferroptosis is a promising combination anticancer strategy. ABSTRACT: Ferroptosis is a programmed death mode that regulates redox homeostasis in cells, and recent studies suggest that it is a promising mode of tumor cell death. Ferroptosis is regulated by iron metabolism, lipid metabolism, and intracellular reducing substances, which is the mechanism basis of its combination with photodynamic therapy (PDT). PDT generates reactive oxygen species (ROS) and (1)O(2) through type I and type II photochemical reactions, and subsequently induces ferroptosis through the Fenton reaction and the peroxidation of cell membrane lipids. PDT kills tumor cells by generating excessive cytotoxic ROS. Due to the limited laser depth and photosensitizer enrichment, the systemic treatment effect of PDT is not good. Combining PDT with ferroptosis can compensate for these shortcomings. Nanoparticles constructed by photosensitizers and ferroptosis agonists are widely used in the field of combination therapy, and their targeting and biological safety can be improved through modification. These nanoparticles not only directly kill tumor cells but also further exert the synergistic effect of PDT and ferroptosis by activating antitumor immunity, improving the hypoxia microenvironment, and inhibiting the tumor angiogenesis. Ferroptosis-agonist-induced chemotherapy and PDT-induced ablation also have good clinical application prospects. In this review, we summarize the current research progress on PDT and ferroptosis and how PDT and ferroptosis promote each other.