| A novel gene transfer system capable of complexing plasmid DNA (pDNA) through complementary hydrogen bonding of guests with base pairs was constructed in this work. Poly(vinyldiaminotriazine) (PVDT) homopolymer and its copolymers with poly(1-vinyl-2-pyrrolidone) were synthesized via conventional radical random polymerization, and water-soluble fractions were collected. These PVDT-based polymers were shown to efficiently complex pDNA and displace ethidium bromide (EB) in EB-intercalated pDNA solutions because of the hydrogen-bonding-induced constrained state of pDNA. It was also found that upon complexation, pDNA seemed to undergo B–C conformation change and circular dichroism spectra assumed a polymer-and-salt-induced (psi)-type pattern that was rationally ascribed to a certain change in the high-order structure of DNA condensates. Transmission electron microscopy presented several morphologies of spheres and toroids within aggregates≥100 nm, resembling DNA condensation induced by cationics. In transfection studies using pDNA-encoding luciferase or enhanced green fluorescent protein, this system could efficiently transfect COS-1 cells. Compared to the commercial polycation system, ExGen 500, these H-bonding vectors displayed several merits such as higher transfection efficiency, lower cytotoxicity, better serum compatibility, and stability in the presence of bovine serum albumin (BSA). The results suggested that PVDT-based polymers are superior to polycation counterparts with regard to their potential in vivo applications.
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