to its degradability, and indeed achieved low cytotoxicity in COS-7 cells
[171]. Complete DNA retardation occurred at weight ratio of 1:1 where the
polyplexes were neutral and therefore aggregated (size >1,300 nm) but efficient
condensation was observed at polymer:DNA ratio of 2:1 (size of the polyplex
<200 nm). Unfortunately the transfection efficiency of these polyplexes was not
reported.
Peptoids (poly-N-substituted glycines) are a class of peptidomimetics whose
side chains are appended to the nitrogen atom of the peptide backbone, rather than
to the α-carbons [172]. Despite their relatively tedious synthesis, there are prospective applications in the biomedical field, for instance in gene therapy [173,
174]. The most efficient peptoid from a vast series as DNA condensing agent was
based on the repetition of N-(2-aminoethyl)glycine (Nae) and N-(2-phenylethyl)
glycine (Npe), (NpeNpeNae) 12 , showing the importance of the presence of primary
amines and hydrophobic motifs [175]. The authors could show that the spacing of
charged residues on the peptoid chain as well as the degree of hydrophobicity of the
side chains had much influence on the ability to form homogeneous complexes with
DNA. Moreover, the authors found that the transfection efficiency was highly
dependent on the primary sequence of the peptoid and, to a lesser degree, on the
length of the peptoid. Zuckermann and colleagues studied another series of peptoids
based on the alternance of primary amine and hydrophobic groups, either phenyl or
isopropyl, and lipitoids (peptoid–phospholipid conjugates) starting from these
peptoids [176]. At charge ratios above unity, only (NpeNpeNae) 12 and
(NaeNpeNpe) 12 and both lipitoids were efficient in inducing transfection, which
was correlated with significant cytotoxicity. Unfortunately, it was not possible in
this study to correlate the physical properties of peptoid/lipitoid:DNA complexes
with their transfection capabilities.
PMMA and Methacrylamide Derivatives
For a series of PAEM homopolymers (Fig. 11a) with various molecular weights
[177], the ability to condense DNA and resistance against heparin destabilization
increased with increasing molecular weight (retardation of DNA in gel electrophoresis at a ratio N:P of 1:1 for PAEM 75 and PAEM 150 , and at a ratio 2:1 for PAEM 45 ).
Regardless of PAEM chain length, the size of the polyplexes were <200 nm for a
wide range of N:P ratio, their zeta potentials at N:P ratio of 8:1 were roughly
similar, as was their cytotoxicity. On one hand, longer PAEM chains enhanced
cellular uptake and nuclear localization of the polyplexes (probably linked to the
greater stability of the polyplexes that might interact more strongly with
membranes, according to the authors), while on the other hand shorter PAEM
chains facilitated intracellular dissociation (more easily displaced from the
polyplex). Nevertheless, even if the ideal carrier should posses both properties,
the polymer with the longest chains also showed the highest transfection
efficiencies in dendritic cells.
PHisA (Fig. 11a) is a water-soluble polymer possessing buffering capacity in the
endosomal pH range [178]. All PHisA polymers with M n in the range of
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
151
[171]. Complete DNA retardation occurred at weight ratio of 1:1 where the
polyplexes were neutral and therefore aggregated (size >1,300 nm) but efficient
condensation was observed at polymer:DNA ratio of 2:1 (size of the polyplex
<200 nm). Unfortunately the transfection efficiency of these polyplexes was not
reported.
Peptoids (poly-N-substituted glycines) are a class of peptidomimetics whose
side chains are appended to the nitrogen atom of the peptide backbone, rather than
to the α-carbons [172]. Despite their relatively tedious synthesis, there are prospective applications in the biomedical field, for instance in gene therapy [173,
174]. The most efficient peptoid from a vast series as DNA condensing agent was
based on the repetition of N-(2-aminoethyl)glycine (Nae) and N-(2-phenylethyl)
glycine (Npe), (NpeNpeNae) 12 , showing the importance of the presence of primary
amines and hydrophobic motifs [175]. The authors could show that the spacing of
charged residues on the peptoid chain as well as the degree of hydrophobicity of the
side chains had much influence on the ability to form homogeneous complexes with
DNA. Moreover, the authors found that the transfection efficiency was highly
dependent on the primary sequence of the peptoid and, to a lesser degree, on the
length of the peptoid. Zuckermann and colleagues studied another series of peptoids
based on the alternance of primary amine and hydrophobic groups, either phenyl or
isopropyl, and lipitoids (peptoid–phospholipid conjugates) starting from these
peptoids [176]. At charge ratios above unity, only (NpeNpeNae) 12 and
(NaeNpeNpe) 12 and both lipitoids were efficient in inducing transfection, which
was correlated with significant cytotoxicity. Unfortunately, it was not possible in
this study to correlate the physical properties of peptoid/lipitoid:DNA complexes
with their transfection capabilities.
PMMA and Methacrylamide Derivatives
For a series of PAEM homopolymers (Fig. 11a) with various molecular weights
[177], the ability to condense DNA and resistance against heparin destabilization
increased with increasing molecular weight (retardation of DNA in gel electrophoresis at a ratio N:P of 1:1 for PAEM 75 and PAEM 150 , and at a ratio 2:1 for PAEM 45 ).
Regardless of PAEM chain length, the size of the polyplexes were <200 nm for a
wide range of N:P ratio, their zeta potentials at N:P ratio of 8:1 were roughly
similar, as was their cytotoxicity. On one hand, longer PAEM chains enhanced
cellular uptake and nuclear localization of the polyplexes (probably linked to the
greater stability of the polyplexes that might interact more strongly with
membranes, according to the authors), while on the other hand shorter PAEM
chains facilitated intracellular dissociation (more easily displaced from the
polyplex). Nevertheless, even if the ideal carrier should posses both properties,
the polymer with the longest chains also showed the highest transfection
efficiencies in dendritic cells.
PHisA (Fig. 11a) is a water-soluble polymer possessing buffering capacity in the
endosomal pH range [178]. All PHisA polymers with M n in the range of
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
151