Employing single valency polyphenol to prepare metal-phenolic network antitumor reagents through FeOOH assistance

Metal-phenolic networks (MPNs) have been conventionally formed by the coordination of metal ions and polyphenols, which can responsively release metal ions and polyphenols under the trigger of tumor microenvironment (TME), showing high potential in the field of antitumor. However, MPNs are mainly limited to multi-valency polyphenols, and the unavailability of single valency polyphenols greatly hinders their applications even though they have excellent antitumor activity. Herein, we demonstrate a FeOOH assisted preparation method for MPNs antitumor reagent by introducing the complexes of Fe3+, H2O and polyphenol (Fe(H2O)x-polyphenoly) in the preparation process, which overcomes the shortage of single valency polyphenols. Taking apigenin (Ap) as an example, Fe(H2O)x-Apy complexes are foremost formed, in which the Fe(H2O)x is capable of hydrolyzing to generate FeOOH, thus producing Fe3+-Ap networks-coated FeOOH nanoparticles (FeOOH@Fe-Ap NPs). Under the stimulation of the TME, FeOOH@Fe-Ap NPs could release Fe2+ and Ap, realizing ferroptosis and apoptosis for tumor combination therapy. In addition, FeOOH can shorten transverse relaxation time, acting as a T2-weighted magnetic resonance imaging contrast agent. The current efforts provide an alternative strategy for constructing MPNs by exploiting single valency polyphenols, which strengthens the potential of MPNs in antitumor applications.