Simultaneous Delivery of Doxorubicin and EZH2 ‐Targeting siRNA by Vortex Magnetic Nanorods Synergistically Improved Anti‐Tumor Efficacy in Triple‐Negative Breast Cancer

A novel nanomedicine is synthesized based on Fe3O4 vortex nanorods loaded with doxorubicin (DOX) and EZH2 siRNAs and coated with a macrophage membrane. It shows a preferential tumor enrichment profile, thus leading to highly efficient drug delivery at the tumor site. Combining chemotherapy and gene therapy exhibits synergistic antitumor activity in a preclinical TNBC model. AbstractTriple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer, currently lacks a targeted therapy and has a high clinical recurrence rate. The present study reports an engineered magnetic nanodrug based on Fe3O4 vortex nanorods coated with a macrophage membrane loaded with doxorubicin (DOX) and Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) siRNA. This novel nanodrug displays excellent tissue penetration and preferential tumor accumulation. More importantly, it significantly increases tumor suppression compared to chemotherapy, suggesting the synergistic activity of the combination of doxorubicin and EZH2-inhibition. Importantly, owing to tumor-targeted delivery, nanomedicine shows an excellent safety profile after systemic delivery, unlike conventional chemotherapy. In summary, chemotherapy and gene therapy are combined into a novel magnetic nanodrug carrying doxorubicin and EZH2 siRNA, which shows promising clinical application potential in TNBC therapy.
Source: Small - Category: Nanotechnology Authors: Tags: Research Article Source Type: research