Stimuli‐Responsive Dendritic Supramolecular Vector for Tumor‐Specific Gene Delivery

To simplify the preparation of dendritic materials, host–guest molecular recognition and self‐assembly are utilized to form a supramolecular dendritic gene vector (DNCVP). DNCVP is constructed from an amino dendron‐conjugated naphthol, viologen containing pH‐sensitive hydrazone‐bond‐linked PEG, and CB[8] with a molar ratio of 1:1:1. The pH‐ and reducing‐sensitivity of DNCVP is verified, and the stimuli‐responsive capacity enables the vector tumor targeting gene delivery ability. Owing to the protection of surface PEG, the supramolecular engineering endows the delivery vector with low cytotoxicity and good biocompatibility that are confirmed by the MTT assay. The excellent delivery ability of genes is investigated by in vitro transfection of pEGFP, pGL3, and silencing of siGAPDH. In vivo studies demonstrate promoted tumor accumulation of genes mediated by the dual‐responsive DNCVP and the transfection efficiency at the tumor site is greatly improved benefiting from the dynamic nature of noncovalent interactions. This study reveals DNCVP is a promising supramolecular dendritic gene delivery vector, providing a sophisticated strategy for precise gene therapy.