Coordination-driven assembly of proteins and nucleic acids in a single architecture for carrier-free intracellular co-delivery

There is intense interest in intracellular co-delivery of functional proteins and nucleic acids for diverse biological research and disease treatment. However, efficient co-encapsulation of these two types of biomacromolecules within a single particle remains an outstanding challenge because of their significantly different characteristics and loading competition inside the particles. Here we report an extremely simple approach to produce a hybrid platform for the co-delivery of proteins and nucleic acids into cancer cells. This system was constructed by one-step, coordination-driven self-assembly of proteins and nucleic acids with metal ions, resulting in spherical hybrid architectures with uniform size, ultrahigh loading content and tunable ratios of the two macromolecular components. The platform enables efficient co-delivery of protein and nucleic acid therapeutics into cells and achieves a significant inhibition of tumor growth in vivo. The simple self-assembly strategy offers an effective tool for the co-delivery of macromolecular therapeutics and has great potential for personalized medicine.