Dibenzocyclooctyne linked lysine-cyclodextrin for efficient intranucleus delivery of proteins

Intranuclear protein delivery shows great prospects in broadening the application scope of protein therapy and revolutionizing medicine, however, effective delivery of native proteins into the nucleus of cells remains a great challenge. Herein, we report the supramolecular nanoparticles based on the self-assembly of dibenzocyclooctyne (DIBO) linked lysine-cyclodextrin (DLC) for efficient intranucleus delivery of proteins. Coordination-driven self-assembly of DLCs in aqueous solution enables efficient encapsulation of proteins just by simple mixing, so as to maintain their biological activity in a reliable way. DLC nanoparticles ensure effective intranuclear protein delivery for therapeutic applications and gene regulation. This rationally designed DIBO containing amino acid-cyclodextrin derivative allows the development of a convenient and universal nanoplatform for intranuclear delivery of native proteins.