cationic albumin proteins yields polypeptides that can fold back into micelle
structures in the presence of lipophilic guest molecules. These micelles can be
taken up by cells due to the presence of multiple positive charges along the
polypeptide backbone, which makes them attractive for drug delivery applications.
A refined polycationic albumin biopolymer has been prepared that bears many drug
molecules attached to the polypeptide backbone. These were protected by the
polypeptide as well as by a second PEO shell, allowing a controlled two-step
drug release. These polycationic polypeptides offer great potential for drug delivery
and simultaneous bioimaging and have already been studied in in vivo experiments.
2 Gene Transfection Utilizing Cationic Cylindrical
Brush Polymers
2.1 Introduction
As described above, cationically modified albumin was successfully utilized in
gene transfection experiments. A novel cylindrical structure of poly-L-lysine (PLL)
in the form of a cylindrical brush polymer with PLL side chains has been utilized
for DNA transfection. The results are compared with the transfection efficiency of
flexible linear PLL/DNA complexes.
Nonviral gene transfection is a widely used in vitro method for studying gene
effects in target cells. However, to date only few successful transfections of brain
endothelial cells have been published [47–49]. For example, Zhang et al. describe
the transfection of murine brain capillary endothelial cells with short polyamines
containing a reducible disulfide backbone [48]. Recently, Chen and colleagues
described a successful downregulation of expression (60% reduction) via targeted
delivery of siRNA-loaded PLGA nanoparticles [50]. Furthermore, another study
compared state-of-the-art transfection approaches and determined that only an
electroporation protocol achieved efficient transfection rates of brain capillary
cells (82% transfected cells) compared to lipid-based transfection (21–40%
transfected cells) [49]. Hence, there is still a high demand for the development of
nonviral gene delivery systems, especially for difficult-to-transfect cell lines like
brain capillary endothelial cells.
Besides viruses [51–57], various synthetic and biological polycation/DNA
complexes have also been utilized as vehicles for gene transport [58–66]. Among
others, the effects of the polycation chemical composition, charge density, and chain
topology (linear flexible coils, hyperbranched or dendritic structures, comb-like
polymers) were investigated [67, 68]. Work on PLL with different chain topologies
(linear, branched, dendritic) by Mannisto ¨ et al. showed no clear relation between the
physicochemical properties (complex size, zeta-potential, condensation of DNA) and
the transfection efficiency [69]. However, linear PLL was more efficient for transfection of D407 cell lines than the dendritic or branched polymer.
Polymer Complexes in Biological Applications
225
structures in the presence of lipophilic guest molecules. These micelles can be
taken up by cells due to the presence of multiple positive charges along the
polypeptide backbone, which makes them attractive for drug delivery applications.
A refined polycationic albumin biopolymer has been prepared that bears many drug
molecules attached to the polypeptide backbone. These were protected by the
polypeptide as well as by a second PEO shell, allowing a controlled two-step
drug release. These polycationic polypeptides offer great potential for drug delivery
and simultaneous bioimaging and have already been studied in in vivo experiments.
2 Gene Transfection Utilizing Cationic Cylindrical
Brush Polymers
2.1 Introduction
As described above, cationically modified albumin was successfully utilized in
gene transfection experiments. A novel cylindrical structure of poly-L-lysine (PLL)
in the form of a cylindrical brush polymer with PLL side chains has been utilized
for DNA transfection. The results are compared with the transfection efficiency of
flexible linear PLL/DNA complexes.
Nonviral gene transfection is a widely used in vitro method for studying gene
effects in target cells. However, to date only few successful transfections of brain
endothelial cells have been published [47–49]. For example, Zhang et al. describe
the transfection of murine brain capillary endothelial cells with short polyamines
containing a reducible disulfide backbone [48]. Recently, Chen and colleagues
described a successful downregulation of expression (60% reduction) via targeted
delivery of siRNA-loaded PLGA nanoparticles [50]. Furthermore, another study
compared state-of-the-art transfection approaches and determined that only an
electroporation protocol achieved efficient transfection rates of brain capillary
cells (82% transfected cells) compared to lipid-based transfection (21–40%
transfected cells) [49]. Hence, there is still a high demand for the development of
nonviral gene delivery systems, especially for difficult-to-transfect cell lines like
brain capillary endothelial cells.
Besides viruses [51–57], various synthetic and biological polycation/DNA
complexes have also been utilized as vehicles for gene transport [58–66]. Among
others, the effects of the polycation chemical composition, charge density, and chain
topology (linear flexible coils, hyperbranched or dendritic structures, comb-like
polymers) were investigated [67, 68]. Work on PLL with different chain topologies
(linear, branched, dendritic) by Mannisto ¨ et al. showed no clear relation between the
physicochemical properties (complex size, zeta-potential, condensation of DNA) and
the transfection efficiency [69]. However, linear PLL was more efficient for transfection of D407 cell lines than the dendritic or branched polymer.
Polymer Complexes in Biological Applications
225