Highly stable and biocompatible hyaluronic acid-rehabilitated nanoscale MOF-Fe 2+ induced ferroptosis in breast cancer cells.

Intracellular amplification of oxidative stress has been proved to be an effective strategy to induce cancer cell death and the Fenton reaction was regarded as a robust way to generate ROS which are the main cause of amplified oxidative stress. However, current Fenton reaction-inducing agents lacked stability in the bio-environment and failed to exert their ideal catalytic performance. We, hereby, designed an Fe2+-based metal-organic framework (MOF) to deliver Fe(2+)to cancer cells to trigger the Fenton reaction and produce excessive ROS. The obtained nano-scale MOF that was constructed by ferrous acetate and organic ligands (BDC-NH2) endowed itself with excellent stability in bio-media and pH responsively degraded itself to release Fe(2+)in the acid tumor microenvironment. Such a characteristic demonstrated robust capacity to catalyze the Fenton reaction and produce considerable ROS and thus induced distinct Fe2+-mediated cell ferroptosis. Meanwhile, directly exploiting an Fe2+-based MOF to inhibit and kill cancer cells circumvented the potential adverse effects of loading drugs (like the cardiotoxicity of doxorubicin, and the nephrotoxicity and ototoxicity of cisplatin) and proved to be biocompatible inin vivoexperiments. More importantly, observations of thein vivoantitumor experiment attested its impressive inhibition on cancer cells and amelioration on the physical health of treated mice. Our study thus presented a novel and biocompatible ferroptosis strategy to be applied in effective clinical cancer therapy.