Controlled synthesis of Zn-doped MnO2 nanoplates for MRI-guided metal ion interference synergistic therapy for breast cancer.

Manganese dioxide (MnO2) nanomaterials have emerged as a promising class of nanoplatform for the therapeutic management of tumors due to their regulable physicochemical properties and good biocompatibility. However, the rational design of MnO2 nanomaterials often decreased the therapeutic efficacy of tumors due to the inherent protective mechanisms of eliminating the imbalance of Mn2+ in cells. Herein, we firstly prepared a novel Zn ion doped MnO2 nanoplate (Zn-MnO2) employing different zeolitic imidazolate framework 8 (ZIF8) precursors as Zn ion source, which possessed enhanced T1-weighted magnetic resonance imaging (MRI) signal, reactive oxygen species (ROS) generation capacity and efficient photothermal conversion. Vitro and vivo experiments proved that the introduction of Zn ion played a key role for therapeutic efficacy of tumors because excessive Zn2+ could be released in tumor, which further promoted apoptosis and ferroptosis of cancer cells. And a series of RNA-seq experiments were carried out to discuss possible anti-cancer mechanism of the as-prepared Zn-MnO2. Obviously, a novel nanoplatform of Zn-doped MnO2 nanoplates was obtained, which could be used for MRI-guided metal ion interference synergistic therapy for breast cancer and provided a paradigm for tumor-specific nanomaterial design.