The development of safe and effective β-cyclodextrin (β-CD)-cored cationic star gene carriers has attracted considerable attention. In this work, a series of star-shaped hemocompatible CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors composed of β-CD cores and piperazine (PP)-, N-(aminoethyl)piperazine (AEPP)-, or N-(3-aminopropyl)-2-pyrrolidinone (APP)-functionalized poly(glycidyl methacrylate) arms were successfully proposed and compared for highly efficient gene delivery. Such star carriers possess plentiful secondary amine, tertiary amine, and nonionic hydroxyl groups. CD-PGPP, CD-PGAEPP, and CD-PGAPP were effective in condensing plasmid DNA into nanoparticles, whose sizes were 100-200 nm and positive ζ potentials were 25-40 mV at nitrogen/phosphate (N/P) ratios of 10 and above. CD-PGPP, CD-PGAEPP, and CD-PGAPP showed significantly lower cytotoxicity than control poly(ethylenimine) (PEI; ∼25 kDa). At most N/P ratios, CD-PGAPP exhibited better gene transfection performance than CD-PGPP and CD-PGAEPP particularly in HepG2 cells. More importantly, in comparison with PEI, all of the CD-PGPP, CD-PGAEPP, and CD-PGAPP vectors did not cause undesirable hemolysis.
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