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.

Developing dedicated nanomedicines to improve delivery efficacy of anti-inflammatory drugs is still a formidable challenge. In this study, we present an extremely simple yet efficient approach to obtain hybrid nanodrugs through metal-drug coordination-driven self-assembly for carrier-free drug delivery. The resulting metallo-nanodrugs exhibit well-defined morphology and high drug encapsulation capability, allowing for the combination of magnetic resonance imaging and anti-inflammatory therapy. In the case of osteoarthritis (OA), the metallo-nanodrugs remarkably alleviate synovial inflammation, preventing cartilage destruction and extracellular matrix loss. In addition, it led to significantly improved therapeutic efficacy compared with intra-articular administration of the same dose of free drugs in OA mouse model. This work provides a very simple approach for the development of anti-inflammatory nanoformulations by exploiting coordination-driven self-assembly.