Delivery System of Nanozymes Loaded with DNAzymes and Hypoxia-Activated Prodrug for Anti-Tumor Metastasis

Breast cancer is a common malignant tumor in women worldwide, and its high metastasis is the main reason for high mortality. Especially under hypoxic microenvironments, the upregulation of hypoxia-inducible factor 1-alpha (HIF-1α) can activate the transcription factor Twist and promote tumor metastasis through epithelial-mesenchymal transformation (EMT). Here, MnO₂ nanosheets are synthesized with oxidase-like activity using fucoidan as a protective agent, and construct a multifunctional delivery system MnO₂@DNAzyme-TPZ (MDT) by loading DNAzymes and hypoxia-activated prodrug Tirapazamine (TPZ) for tumor treatment and metastasis inhibition. MDT kills tumors by converting O₂ into reactive oxygen species (ROS) through MnO₂ nanozymes, and inhibits tumor metastasis by selectively silencing the tumor metastasis-related Twist gene through DNAzymes. TPZ enhances tumor killing under hypoxic environments and synergistically inhibits tumor metastasis by reducing the expression of HIF-1α. MDT significantly inhibits tumor growth and metastasis in vivo in an in situ tumor model. The strategy of combining selective gene silencing based on DNAzymes with nanozymes and hypoxia-activated prodrug provides a new approach to anti-tumor metastasis therapy.