Tremella-Derived MnO2 Nanoflowers for Tumor-Cell-Responsive Imaging and Combined Gene-Photodynamic Actions In Vitro

A green and biocompatible strategy for synthesizing MnO 2 nanoflowers is reported using Tremella fuciformis as a natural reductant and structural template. The resulting MnO 2 was employed as a redox-responsive carrier for constructing a multifunctional DNA nanodevice (X-DMNF) integrating tumor-cell imaging, dual-gene regulation, and photodynamic activity. The X-DNA scaffold incorporated miR-21 recognition elements, Mn 2+ -activated DNAzymes targeting EGR-1 and Survivin mRNA, and a Ce6 photosensitizer. Upon cellular internalization, endogenous glutathione (GSH) triggered MnO 2 degradation, releasing Mn 2+ and restoring fluorescence for miRNA detection. The released DNAzymes catalyzed selective mRNA cleavage, while Ce6 generated singlet oxygen under laser irradiation. In vitro experiments demonstrated efficient miRNA recognition, gene silencing, reactive oxygen species generation, and synergistic cytotoxicity in MCF-7 cells, with minimal off-target effects on normal cells. This work establishes a green and modular approach for constructing GSH-responsive DNA-MnO 2 nanodevices and provides a promising platform for cell-level cancer diagnostics and mechanistic therapeutic studies, pending future in vivo validation.