3.1.3 Polysulfobetaines
Polymers based on a sulfobetaine and the triblock thereof, PSB-b-POEMA-b-PSB
(Fig. 23e) were found to be able to complex DNA [232]. The approach relied on
OEMA as steric stabilizer, while the zwitterionic sulfobetaine itself was supposed
to complex DNA, despite the presence at a short distance of the quaternary
ammonium in the middle of the chain and the sulfonate as chain end (electrostatic
repulsion with DNA). Nevertheless, its potential interest relied in the schizophrenic
behavior of the polymer: the poly{N-[3-(methacryloylamino)propyl]-N,Ndimethyl-N-(3-sulfopropyl) ammonium hydroxide}block possessing an UCST (as
heat energy is required to dissociate the crosslinking points stemming from ion
pairings between ammonium cation and sulfo anion), whereas the poly
[2-(2-methoxyethoxy)ethyl methacrylate] possessed an LCST. In the series
obtained at 1 wt%, the polymers possessed an UCST in the range 14–18
C,
followed by an LCST in the range 22–24
C (both transitions are dependent on
the length of the blocks and concentration of the polymers in solution, in the range
of DP considered for the PSB block and for the POEMA block with DP of 160 and
less). The homopolymer PSB 200 quenched 75% of EtBr fluorescence at polymer:
DNA ratio of 5 and completely quenched it at N:P ratio of 20. The polymer
condensed DNA into nanoparticles of less than 80 nm in diameter. PSB 50 -bPOEMA 100 -b-PSB 50 and PSB 80 -b-POEMA 40 -b-PSB 80 both quenched 40–45%
of the fluorescence at ratio of 5, and reached a plateau of 55–60% at a ratio of 20.
At a ratio of 10, they formed NPs with average size of 120 nm that were less
compact and with irregular shape. This superior quenching of EtBr fluorescence
cannot only be explained by the distance between opposite charges if we refer to the
case of polycarboxybetaine. The capacity of the copolymers to bind DNA
decreased with a decrease in the relative proportion of the PSB block (decrease in
charge density) as well as an increase in the proportion of POEMA (steric
hindrance).
3.2 Polyamphoters
An amphoteric species is a molecule or ion that can react as an acid as well as a
base. One type of amphoteric species are amphiprotic molecules, which can either
donate or accept a proton; examples are amino acids and proteins, which have
amine and carboxylic groups. The competition between the acid–base equilibria of
these groups leads to additional “complications” in their physical behavior but can
also present some advantages due to the variation of their charge as a function
of pH.
Poly(1,2-propylene H-phosphonate) modified with spermidine (PPA-g-SP,
Fig. 24a with m ¼ 1) had a LD 50 of 85 μg mL
À1 in HEK293 and COS-7 cells
[233]. Efficient complexation with DNA was achieved for N:P ratios of 1.5 and
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
179
Polymers based on a sulfobetaine and the triblock thereof, PSB-b-POEMA-b-PSB
(Fig. 23e) were found to be able to complex DNA [232]. The approach relied on
OEMA as steric stabilizer, while the zwitterionic sulfobetaine itself was supposed
to complex DNA, despite the presence at a short distance of the quaternary
ammonium in the middle of the chain and the sulfonate as chain end (electrostatic
repulsion with DNA). Nevertheless, its potential interest relied in the schizophrenic
behavior of the polymer: the poly{N-[3-(methacryloylamino)propyl]-N,Ndimethyl-N-(3-sulfopropyl) ammonium hydroxide}block possessing an UCST (as
heat energy is required to dissociate the crosslinking points stemming from ion
pairings between ammonium cation and sulfo anion), whereas the poly
[2-(2-methoxyethoxy)ethyl methacrylate] possessed an LCST. In the series
obtained at 1 wt%, the polymers possessed an UCST in the range 14–18
C,
followed by an LCST in the range 22–24
C (both transitions are dependent on
the length of the blocks and concentration of the polymers in solution, in the range
of DP considered for the PSB block and for the POEMA block with DP of 160 and
less). The homopolymer PSB 200 quenched 75% of EtBr fluorescence at polymer:
DNA ratio of 5 and completely quenched it at N:P ratio of 20. The polymer
condensed DNA into nanoparticles of less than 80 nm in diameter. PSB 50 -bPOEMA 100 -b-PSB 50 and PSB 80 -b-POEMA 40 -b-PSB 80 both quenched 40–45%
of the fluorescence at ratio of 5, and reached a plateau of 55–60% at a ratio of 20.
At a ratio of 10, they formed NPs with average size of 120 nm that were less
compact and with irregular shape. This superior quenching of EtBr fluorescence
cannot only be explained by the distance between opposite charges if we refer to the
case of polycarboxybetaine. The capacity of the copolymers to bind DNA
decreased with a decrease in the relative proportion of the PSB block (decrease in
charge density) as well as an increase in the proportion of POEMA (steric
hindrance).
3.2 Polyamphoters
An amphoteric species is a molecule or ion that can react as an acid as well as a
base. One type of amphoteric species are amphiprotic molecules, which can either
donate or accept a proton; examples are amino acids and proteins, which have
amine and carboxylic groups. The competition between the acid–base equilibria of
these groups leads to additional “complications” in their physical behavior but can
also present some advantages due to the variation of their charge as a function
of pH.
Poly(1,2-propylene H-phosphonate) modified with spermidine (PPA-g-SP,
Fig. 24a with m ¼ 1) had a LD 50 of 85 μg mL
À1 in HEK293 and COS-7 cells
[233]. Efficient complexation with DNA was achieved for N:P ratios of 1.5 and
Polyelectrolyte Complexes of DNA and Polycations as Gene Delivery Vectors
179