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

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.

Mitochondrial-Targeted Copper Delivery for Cuproptosis-Based Synergistic Cancer Therapy.

Cuproptosis is dependent on mitochondrial respiration modulation by targeting lipoylated tricarboxylic acid cycle (TCA) cycle proteins, showing great potential in cancer treatment. However, the specific release of copper ions at mitochondrial is highly needed and still a major challenge to trigger cellular cuproptosis. Herein, a metal-organic framework-based nanoplatform (ZCProP) is designed for mitochondrial-targeted and ATP/pH-responsive Cu and prodigiosin release.

Synergistic glycolysis disturbance for cancer therapy by a MOF-based nanospoiler.

Increased glycolysis for promoting adenosine triphosphate (ATP) generation is one of the hallmarks of cancer. Although reducing glucose intake or depriving cellular glucose can delay the growth of tumors to some extent, their therapeutic efficacy is a highly needed improvement for clinical translation. Herein, we found that mannose synergistic with glucose oxidase (GOx) can induce cell death by ATP inhibition, autophagy activation, and apoptosis protein upgradation.