DNA Tetrahedron Nanodevice as a Co-delivery Vehicle of Shikonin and CpG Oligonucleotide for Enhanced Triple-Negative Breast Cancer Chemoimmunotherapy

DNA tetrahedron (DT) nanostructures have shown broad application prospects in disease diagnosis and treatment due to their structural programmability, nontoxicity, and efficient cellular uptake. Recently, their potential as ideal nanocarriers for synergistic anticancer drug delivery has been increasingly recognized. In this study, the first use of a DT nanostructure to co-deliver shikonin (SK) and CpG oligonucleotide to achieve chemoimmunotherapy of triple-negative breast cancer (TNBC) is reported. In this nanoplatform, SK serves as both a cytotoxic agent and an immunogenic cell death (ICD) inducer, while CpG-modified DT (CpG-DT) has dual functions of drug carrier and immune adjuvant, which can significantly enhance the ICD effect. CpG-DT/SK exhibits an enhanced water solubility and tumor-specific accumulation. The synergistic combination of SK and CpG further facilitated the maturation of dendritic cells and the subsequent infiltration of CD8+ and CD4+ T cells, thereby achieving effective inhibition of 4T1 tumor growth. This DT-based co-delivery nanoplatform provides a promising strategy for TNBC treatment with great potential for clinical translation.