Iron (II)-based metal-organic framework nanozyme for boosting tumor ferroptosis through inhibiting DNA damage repair and system Xc-

Abstract

Development of ferroptosis-inducible nanoplatforms with high efficiency and specificity is highly needed and challenging in tumor ferrotherapy. Here, we demonstrate highly effective tumor ferrotherapy using iron (II)-based metal-organic framework (FessMOF) nanoparticles, assembled from disulfide bonds and ferrous ions. The as-prepared FessMOF nanoparticles exhibit peroxidase-like activity and pH/glutathione-dependent degradability, which enables tumor-responsive catalytic therapy and glutathione depletion by the thiol/disulfide exchange to suppress glutathione peroxidase 4, respectively. Upon PEGylation and Actinomycin D (ActD) loading, the resulting FessMOF/ActD-PEG nanoplatform induces marked DNA damage and lipid peroxidation. Concurrently, we found that ActD can inhibit Xc− system and elicit ferritinophagy, which further boosts the ferrotherapeutic efficacy of the FessMOF/ActD-PEG. In vivo experiments demonstrate that our fabricated nanoplatform presents excellent biocompatibility and a high tumor inhibition rate of 91.89%.

Ferroptosis: a novel mechanism of cell death in ophthalmic conditions

“…Cysteine metabolism plays a pivotal role in ferroptosis, serving as a critical regulatory hub for the synthesis of GSH, the primary antioxidant defense against the peroxidation of lipids within the cell membrane. The cystine/glutamate antiporter System Xc- is a complex composed of two subunits, the light chain (SLC7A11) and the heavy chain (SLC3A2), which are linked by disulfide bonds ( 46 ). This transporter plays a vital role in cellular antioxidant defense mechanisms.…”