A double DNAzyme-loaded MnO2 versatile nanodevice for precise cancer diagnosis and Self-Sufficient synergistic gene therapy

Tumors progression is usually characterized by proliferation, migration, and angiogenesis, and it leads to uncontrolled tissue growth and blocks the mechanism of apoptosis. Therefore, targeted angiogenesis and anti-apoptosis is considered promising therapeutic strategy for cancer prevention and treatment. Herein, we report a versatile and intelligent MnO2-PEI-DNAzymes (MnPDs) nanodevice for self-sufficient anti-tumor angiogenesis and pro-apoptosis synergistic gene silencing, coupling multi-target bimodal in situ imaging. Intracellularly, the multifunctional charge-reversal MnPDs undergo reduction and lysis by the overexpressed GSH, actualizing enhanced MR imaging and sufficient DNAzyme cofactors in tumor tissue, and enabling miRNA-155 and telomerase biomarkers dual-fluorescence imaging. Under the precise multimodal imaging, the dual DNAzymes enable self-sufficient Early growth response-1 (EGR1) and Survivin (SUR) mRNAs synergistic silencing, effectively inhibiting tumor angiogenesis and anti-apoptotic. Considering that accurate and efficient therapy has become a trend in cancer therapy, our proposed self-sustaining multifunctional nanodevice is promising for broad clinical applications.