An Electron Donor-Acceptor Structured Rhenium(I) Complex Photo-sensitizer Evokes Mutually Reinforcing "Closed-Loop" Ferroptosis and Immunotherapy.
Qingyan RenHaobing WangDan LiAnyi DaoJiajun LuoDeliang WangPingyu ZhangHuaiyi HuangPublished in: Advanced healthcare materials (2024)
The hypoxic microenvironment of solid tumors severely lowers the efficacy of oxygen-dependent photodynamic therapy (PDT). The development of hypoxia-tolerant photosensitizers for PDT is an urgent requirement. In this study, we report a novel rhenium complex (Re-TTPY) to develop a "closed-loop" therapy based on PDT-induced ferroptosis and immune therapy. Due to its electron donor-acceptor (D-A) structure, Re-TTPY undergoes energy transfer and electron transfer processes under 550 nm light irradiation, and displays hypoxia-tolerant type I/II combined PDT capability, which can generate 1 O 2 , O 2 ·- , and ·OH simultaneously. Furthermore, the reactive oxygen species (ROSs) lead to the depletion of 1,4-dihydronicotinamide adenine dinucleotide (NADH), glutathione peroxidase 4 (GPX4) and glutathione (GSH). As a result, ferroptosis occurs in cells, simultaneously triggers immunogenic cell death (ICD) and promotes the maturation of dendritic cells (DCs) and infiltration of T cells. The release of interferon-γ (IFN-γ) by CD8+ T cells downregulates the expression of GPX4, further enhances the occurrence of ferroptosis, thereby forming a mutually reinforcing "closed-loop" therapeutic approach. This article is protected by copyright. All rights reserved.
Keyphrases
- photodynamic therapy
- cell death
- electron transfer
- cell cycle arrest
- dendritic cells
- energy transfer
- fluorescence imaging
- solar cells
- reactive oxygen species
- immune response
- endothelial cells
- poor prognosis
- quantum dots
- induced apoptosis
- regulatory t cells
- risk assessment
- high glucose
- signaling pathway
- radiation therapy
- diabetic rats
- drug induced
- radiation induced
- cell therapy
- mesenchymal stem cells