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

Abstract

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.

Metal‐Organic Framework‐Based Nanomedicines for Ferroptotic Cancer Therapy

“…ROS production is a common pathway for ferroptosis therapy, sonodynamic therapy (SDT), and photodynamic therapy (PDT). [80,81] TCPP, a member of the porphyrin family of macromolecular heterocyclic compounds, is capable of generating ROS upon light/acoustic stimulation. [72,82] Importantly, TCPP can be liganded with metal ions to form MOF without additional modification.…”

Recent advances in the nanoarchitectonics of metal–organic frameworks for light-activated tumor therapy

“…41 Also, when using nMOFs as a carrier in vivo , they can be captured by immune cells such as Macrophage; in order to maximize the therapeutic effect, it is also highly desirable to realize their abilities to target specific tumors and evade immune clearance. 121,122 Much effort has been devoted to decreasing immune clearance through the conjugation of specific targeting moieties on the MOF's surface, such as folate, antibodies, and peptides, but complex preparations have frequently restricted such approaches, which still needs to be deeply explored.…”

Application of singlet oxygen-activatable nanocarriers to boost X-ray-induced photodynamic therapy and cascaded ferroptosis for breast cancer treatment

“…PDT also promotes ferroptosis by non-enzymatic lipid peroxidation and sensitizes the tumor cells to ferroptosis via immunological effects. [33][34][35][36] For instance, Yu et al reported an acidity activated micelle for PPa-involved PDT, and the recruited tumor-infiltrating T lymphocytes further benefited the treatment of cancer cells with RSL3-inducible ferroptosis to inhibit the growth of melanoma and metastatic breast tumors. 12 Hao et al tailored HEK293T cell-secreted exosomes that overexpressed CD47 to escape recognition by the mononuclear phagocyte system and induce ferroptosis following 532 nm laser-excited PDT.…”