Engineering hierarchical metal-organic@metal-DNA heterostructures for combinational tumor treatment

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.