Visible Light-Guided Gene Delivery with Nonviral Supramolecular Block Copolymer Vectors.

To achieve efficient gene delivery in vitro or in vivo , nonviral vectors should have excellent biostability across cellular and tissue barriers and also smart stimuli responsiveness toward controlled release of therapeutic genes into the cell nucleus. However, it remains a key challenge to effectively combine the biostability of covalent polymers with the stimuli responsiveness of noncovalent polymers into one nonviral vehicle. In this work, we report the construction of a kind of cationic supramolecular block copolymers (SBCs) through noncovalent polymerization of β-cyclodextrin/azobenzene-terminated pentaethylenehexamine (DMA-Azo-PEHA-β-CD) in aqueous media using β-CD-monosubstituted poly(ethylene glycol) (PEG-β-CD) as a supramolecular initiator. The resultant SBC exhibits superior biostability, biocompatibility, and light/pH dual-responsive characteristics, and it also demonstrates efficient plasmid DNA condensation capacity and the ability to rapidly release plasmid DNA into cells driven by visible light (450 nm). Eventually, this SBC-based delivery system demonstrates visible light-induced enhancement of gene delivery in both COS-7 and HeLa cells. We anticipate that this work provides a facile and robust strategy to enhance gene delivery in vitro or in vivo via visible light-guided manipulation of genes, further achieving safe, highly efficient, targeting gene therapy for cancer.