Hyperbranched glycoconjugated polymer from natural small molecule kanamycin as a safe and efficient gene vector

The exploration of safe and efficient polycationic gene vectors from natural small molecules such as kanamycin was proposed. Cationic hyperbranched glycoconjugated polymer was synthesized by the Michael-addition polymerization of kanamycin and N,N′-methylenebisacrylamide, and the resultant product was well characterized by FTIR, 1H NMR, 13C NMR, SEC-MALLS and ζ-potential analyses. The nitrogen content (7.3%) of this kanamycin-based hyperbranched glycoconjugated polymer was much lower than that (32.6%) of polyethylenimine (PEI) control. Moreover, this resultant polymer could be degraded in acidic conditions. Therefore, the hyperbranched glycoconjugated polymer showed low cytotoxicity, even lower than that of natural biomacromolecule chitosan. Due to the existence of various primary, secondary and tertiary amines in the polymer backbone, hyperbranched glycoconjugated polymer exhibited high buffering capacity and strong pDNA condensation ability. In vitro transfection showed that the luciferase expression of hyperbranched glycoconjugated polymer was about 4.4 × 108 RLU per mg protein, approximately 33-fold greater than that of chitosan transfection. These results demonstrate that the construction of highly branched polycations from natural small molecules provides a new opportunity for developing safe and efficient gene vectors.