Efficient delivery of therapeutics to immune cells remains a formidable challenge for cancer immunotherapy. In this work, we demonstrate that an aptamer-driven DNA nanodevice, constructed through linkage of a synthetic immunostimulant (Toll-like receptor 9 agonist: CpG motif) to an aptamer, could significantly enhance the immunostimulatory activity by facilitating the uptake and retention of therapeutics in macrophages. Systemic administration of the DNA nanodevice results in efficient tumor growth inhibition in both breast cancer and melanoma mouse models. Our studies suggest that the DNA nanodevice leads to re-education of tumor-associated macrophages and ultimately to reversing the tumor immune microenvironment. The strategy for aptamer-mediated and vehicle-free delivery of immunostimulatory oligonucleotides provides a potential platform for cancer immunotherapy.

Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks (MOFs) is important for various biomedical applications, yet remains a challenge. Herein, a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and Fe^II ions on nanoscale MOFs, resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers. The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability. By incorporation of a chemotherapeutic drug into the Fe-DNA shell, the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment. Moreover, the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen, which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome. This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.