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.

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.