bears two ammonio groups per monomer instead of one, it was found that the
properties of the polyplexes were remarkably similar, suggesting that after reaching
a certain density of positive charges, the effects (DNA condensation, cytotoxicity,
etc.) might plateau. The effect of charge dilution was addressed using random
copolymers containing TMAEM.Cl and HPMA as monomers. All these copolymers
(TMAEM.Cl, 5–75%) were capable of binding DNA, although copolymers with
greater than 50% TMAEM.Cl content were not capable of forming particulate
complexes (as shown by AFM). According to the authors, it seems likely that
these copolymers could not drive hydrophobic self-assembly of polymer/DNA
complexes (because of the presence of hydrophilic HPMA). Moreover, the
complexes based on these random copolymers showed low levels of transfection
similar to the parent PTMAEM.Cl, but also poor ability to undergo transcription
following intranuclear injection, which may be due to the steric protection of the
DNA from polymerases by the presence of HPMA. Finally, the influence of cationic
polymer molecular weight on the properties of complexes formed with DNA was
examined and there were some indications of the effects of molecular weight on
transfection activity against HEK 293 cells for many of the polymers examined in
this study. PVA.HCl, PMAEDA.HCl, PMAGEDA.HCl, and PTMAEM.Cl:DNA
complexes formed with higher molecular weight cationic polymer often showed
greater expression of reporter genes, which was usually also linked to an increased
cytotoxicity.
With Steric Stabilizer
Most of the publications on polycations for DNA condensation possessing a steric
stabilizer deal with the influence of the polymer architecture on the properties of
the polyplexes (physico-chemical characteristics and transfection efficiency). Two
types of architectures are mainly studied: linear copolymers with block and/or
graft (eventually brush) architectures (Scheme 17). The steric stabilizers most
commonly used are based on ethylene glycol or contain hydroxyl groups such as
hydroxyethyl methacrylate or sugars (only a few examples are presented here
because sugar-based polycations are out of the scope of this review).
PDMAEMA Derivatives
For PDMAEMA-b-PEG (Fig. 12a), PDMAEMA-b-POEGMA, and P(DMAEMAstat-PEGMA) (Fig. 12b) of relatively low M n (7.8–21 kDa), the introduction of
PEG did not significantly reduce the buffering capacity of PDMAEMA-based
copolymers (for equivalent contents of DMAEMA units), but logically the buffering capacity is dependent on the DMAEMA content [182]. Of these polymers,
the comb-type PDMAEMA-stat-PEGMA had the best complexing properties
because charge neutrality was reached at a lower monomer:nucleotide molar
ratio, which could be explained by its higher content of DMAEMA units compared
to the other polymers (66% versus 30–37%). The steric effect of PEG chains
154
A. Bertin
properties of the polyplexes were remarkably similar, suggesting that after reaching
a certain density of positive charges, the effects (DNA condensation, cytotoxicity,
etc.) might plateau. The effect of charge dilution was addressed using random
copolymers containing TMAEM.Cl and HPMA as monomers. All these copolymers
(TMAEM.Cl, 5–75%) were capable of binding DNA, although copolymers with
greater than 50% TMAEM.Cl content were not capable of forming particulate
complexes (as shown by AFM). According to the authors, it seems likely that
these copolymers could not drive hydrophobic self-assembly of polymer/DNA
complexes (because of the presence of hydrophilic HPMA). Moreover, the
complexes based on these random copolymers showed low levels of transfection
similar to the parent PTMAEM.Cl, but also poor ability to undergo transcription
following intranuclear injection, which may be due to the steric protection of the
DNA from polymerases by the presence of HPMA. Finally, the influence of cationic
polymer molecular weight on the properties of complexes formed with DNA was
examined and there were some indications of the effects of molecular weight on
transfection activity against HEK 293 cells for many of the polymers examined in
this study. PVA.HCl, PMAEDA.HCl, PMAGEDA.HCl, and PTMAEM.Cl:DNA
complexes formed with higher molecular weight cationic polymer often showed
greater expression of reporter genes, which was usually also linked to an increased
cytotoxicity.
With Steric Stabilizer
Most of the publications on polycations for DNA condensation possessing a steric
stabilizer deal with the influence of the polymer architecture on the properties of
the polyplexes (physico-chemical characteristics and transfection efficiency). Two
types of architectures are mainly studied: linear copolymers with block and/or
graft (eventually brush) architectures (Scheme 17). The steric stabilizers most
commonly used are based on ethylene glycol or contain hydroxyl groups such as
hydroxyethyl methacrylate or sugars (only a few examples are presented here
because sugar-based polycations are out of the scope of this review).
PDMAEMA Derivatives
For PDMAEMA-b-PEG (Fig. 12a), PDMAEMA-b-POEGMA, and P(DMAEMAstat-PEGMA) (Fig. 12b) of relatively low M n (7.8–21 kDa), the introduction of
PEG did not significantly reduce the buffering capacity of PDMAEMA-based
copolymers (for equivalent contents of DMAEMA units), but logically the buffering capacity is dependent on the DMAEMA content [182]. Of these polymers,
the comb-type PDMAEMA-stat-PEGMA had the best complexing properties
because charge neutrality was reached at a lower monomer:nucleotide molar
ratio, which could be explained by its higher content of DMAEMA units compared
to the other polymers (66% versus 30–37%). The steric effect of PEG chains
154
A. Bertin