Functional Polymers for Gene Delivery - Functional Polymers for Nanomedicine - page 103

von Erlach et al. investigated different copolymers of poly( L -lysine)-graft-
poly(2-methyl-2-oxazoline) (PLL-g-PMOXA) of variable grafting densities
and PMOXA molecular weights for their potential to complex and deliver
plasmid DNA. 134 Good transfection efficiency combined with low cytotoxicity
of PLL-g-PMOXA-DNA condensates was demonstrated in COS-7 cells. This
suggested that DNA-PMOXA-g-PLL condensate formation for efficient DNA
delivery strongly depended on the PMOXA grafting density and molecular
weight.
Poly(b-amino esters) (PBAEs) are a new class of polymeric vectors first
developed by Lynn et al. 135,136 The main advantage offered by PBAEs over
PEI is their biodegradability via the hydrolytically cleavable ester groups.
Using high-throughput synthesis and parallel screening, a large library of
PBAEs was created that helped to elucidate the effect of small changes in
polymer structure on transfection efficiency. 137,138 Recently, Bhise et al.
developed novel gene delivery vectors for efficient gene transfer to hard-to-
transfect mouse mammary epithelial cells. 139 Ten modified versions of the
same base PBAEs, poly(butane-1,4-diol diacrylate-co-5-aminopentan-1-ol),
were synthesized. Small modifications to the polymer end-capping molecules
and tuning of the polymer molecular weight could either significantly enhance
the transfection efficacy up to six-fold or instead abolish efficacy completely.
These degradable polymers were more effective than FuGENE HD for gene
delivery in both 2-D culture and 3-D organotypic culture, and could be used as
reagents and therapeutics for breast cancer. Tzeng et al. found that PBAEs
could transfect glioblastoma 319 astrocytes with comparable or superior
efficiency and safety compared to leading commercial reagents (Lipofectamine
2000 and FuGENE HD) (Scheme 4.20). 140
Recently, Zhang et al. developed a new class of cationic transfection agents
based on cationic shell-crosslinked knedel-like nanoparticles (cSCKs) that
efficiently transfect mammalian cells with both oligonucleotides and plasmid

d n 4 y 3 n g | 3

Scheme 4.20

Synthesis of poly(b-amino esters) (PBAEs).