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. Coordination-driven self-assembly of dibenzocyclooctyne (DIBO) linked lysine-cyclodextrin (DLC) in aqueous solution enables efficient encapsulation of proteins just by simple mixing, so as to maintain their biological activity and ensure effective intranuclear protein delivery for therapeutic applications and gene regulation. [Display omitted] •Dibenzocyclooctyne (DIBO) linked lysine-cyclodextrin (DLC) for effective intranucleus protein delivery has been prepared.•DLC can self-assemble into nanoparticles in aqueous solution and achieve superior encapsulation of various proteins.•DLC proves to be a universal nanocarrier that can deliver various proteins directly into the nucleus.•Nrf2 delivered with targeted DLC nanoparticles could regulate gene expressions in vivo.