Recent progress in cancer therapy based on the combination of ferroptosis with photodynamic therapy

Current anticancer treatments have many limitations to achieving high efficacy. Hence, novel strategies that broaden therapeutic prospects must urgently be developed. Ferroptosis is an iron-dependent form of non-apoptotic programmed cell death that is induced by cellular antioxidative system inhibition. Photodynamic therapy (PDT) uses photosensitizers to generate reactive oxygen species and aggravate oxidative stress in tumor cells. Combining ferroptosis with PDT cooperatively regulates intracellular redox homeostasis, thus increasing cancer cell susceptibility to oxidative stress and yielding synergistic anticancer effects. In this review, various strategies for combining ferroptosis with PDT are comprehensively summarized and discussed, including mono-PDT and PDT-induced ferroptosis, combining PDT with small-molecule ferroptosis inducers, and combining PDT with metal-ion-induced ferroptosis. Additionally, the possibility of combining ferroptosis and PDT with other anti-tumor therapies is discussed. Finally, the prospects and challenges of combining ferroptosis with PDT in clinical cancer treatment are addressed. With increased understanding of the superiority of combination PDT with ferroptosis for cancer treatment, we hope that drug delivery systems based on this strategy will be further developed to increase anticancer efficiency and achieve successful clinical translation.