Fe(II) and tannic acid-cloake MOF as carrier of artemisinin for supply of ferrous ions to enhance treatment of triple-negative breast cancer

Abstract Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer (TNBC), which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Poor water solubility and insufficient availability of intracellular ferrous ions, limit the further application of ART in antitumor therapy. In this study, ferrous-supply nanocarrier was constructed based on tannic acid (TA) and ferrous ion (Fe2+)-coated on the zeolitic imidazolate framework-8(ZIF) with ART encapsulated (TA-Fe/ART@ZIF). via supramolecular coordination. Following the internalization of the as-prepared nano-system in cells, acidic degradation of the vehicles would facilitate the release of ART and accumulation of Fe2+. The results revealed that the newly developed nano-drug system displayed a high level of intracellular ROS generation, and markedly enhanced ferroptosis. This work provides a novel approach to enhance the potency of ferroptotic nanomedicine and new directions for TBNC therapy.