Host–Guest‐Mediated DNA Templation of Polycationic Supramolecules for Hierarchical Nanocondensation and the Delivery of Gene Material

摘要: Only a few examples of monodisperse molecular entities that can compact exogenous nucleic acids into nanocomplexes, protect the cargo from biological environment, facilitate cell internalization, and promote safe transfection have been reported up to date. Although these species open new venues for fundamental studies on structural requirements govern intervening processes their application in nonviral gene-vector design, synthesis moieties generally requires relatively sophisticated chemistry, which hampers further development gene therapy. Herein, we report an original strategy reversible complexation delivery DNA based supramolecular preorganization β-cyclodextrin-scaffolded polycationic cluster facilitated by bisadamantane guests. The resulting gemini-type, dual-cluster supramolecules then undergo DNA-templated self-assembly at neutral pH value bridging parallel oligonucleotide fragments. This hierarchical condensation mechanism affords transfectious nanoparticles with buffering capabilities, thus facilitating endosomal escape following internalization. Protonation also destabilizes dimers consequently whole edifice, assisting release. Our advanced hypotheses are supported isothermal titration calorimetry, NMR circular dichroism spectroscopic analysis, gel electrophoresis, dynamic light scattering, TEM, mechanics, dynamics, conducted vitro vivo.