Folic‐Acid‐Targeted Self‐Assembling Supramolecular Carrier for Gene Delivery

A targeting gene carrier for cancer-specific delivery was successfully developed through a multilayer bricks-mortar strategy. The gene carrier was composed of adamantane-functionalized folic acid (FA-AD), an adamantane-functionalized poly(ethylene glycol) derivative (PEG-AD), and -cyclodextrin-grafted low-molecular-weight branched polyethylenimine (PEI-CD). Carriers produced by two different self-assembly schemes, involving either precomplexation of the PEI-CD with the FA-AD and PEG-AD before pDNA condensation (Method A) or pDNA condensation with the PEI-CD prior to addition of the FA-AD and PEG-AD to engage host-guest complexation (Method B) were investigated for their ability to compact pDNA into nanoparticles. Cell viability studies show that the material produced by the Method A assembly scheme has lower cytotoxicity than branched PEI 25 kDa (PEI-25KD) and that the transfection efficiency is maintained. These findings suggest that the gene carrier, based on multivalent host-guest interactions, could be an effective, targeted, and low-toxicity carrier for delivering nucleic acid to target cells.