Cationic polymers, cationic polymer functionalized metal
nanoparticles, cationic lipids, or cationic lipids assembled into
lipid bilayer vesicles or liposomes, expose their positively charged
amine group/s to the aqueous medium, which electrostatically
bind to DNA and other nucleic acids such as small interfering
RNA (siRNA) and messenger RNA (mRNA). These amine groups
are the nucleic acid binding moieties, and upon electrostatic interaction, condense these carriers into smaller transportable units,
termed lipoplexes for lipid-based complexes, or polyplexes for
polymer-based complexes [2, 3]. Due to the small or nano-size of
these complexes (including the inorganic nanoparticles), we shall
refer to all such complexes as nanocomplexes.
Polymers such as dendrimers [4, 5], chitosan [6, 7], poly-Llysine (PLL) [7, 8], and polyethyleneimine (PEI) [9, 10] have
gained much interest due to their ability to bind and condense
DNA and have hence been a popular choice for cationic functionalization of inorganic nanoparticles [11]. Hence, these interactions
are mostly ionic in nature. Nanocomplexes can be dynamic in
nature, and depending on the formulation conditions different
conformations may arise. This chapter looks mostly at electrostatic
formulations, with one of the first simplistic models of this type
described by Felgner and Ringold in 1989 for the interaction of
cationic liposomes with plasmid DNA [12], where a single plasmid
is trapped within four liposomes. However, considering the different isoforms especially the supercoiled forms of the DNA, likely
structures that can occur are those resembling the nanoparticles
clustered like grapes around a more branched DNA molecule [13],
or a “bead on a string” conformation [14], or a “spaghetti-meatball” type appearance [15]. In all cases, the cationic nanoparticles
will continually bind to the DNA until a critical point (optimal
binding ratio) is attained.
In the case of inorganic and metal nanoparticles, depending on
the type of synthesis, they can adopt various shapes, such as rods,
spheres, diamonds, stars, cubes, and triangles among others. Cellular uptake can be dependent on shape due to differences in the
particle curvature, which ultimately influences the particle contact
area with the cell membrane [16, 17]. While most studies have
indicated that spherical nanoparticles have a higher propensity to be
internalized in vitro in epithelial cells compared to rod-shaped
particles of similar dimensions [18, 19], a contrasting study has
shown that rod-shaped nanoparticles are more readily taken up by
intestinal epithelial cells, in vitro, than spherical nanoparticles
[17]. However, these two conformations seem most favorable
and hence popular as nanodelivery vehicles. Hence, it is crucial to
fully examine these formulations and their optimal binding prior to
use in vitro or in vivo.
44
Moganavelli Singh
nanoparticles, cationic lipids, or cationic lipids assembled into
lipid bilayer vesicles or liposomes, expose their positively charged
amine group/s to the aqueous medium, which electrostatically
bind to DNA and other nucleic acids such as small interfering
RNA (siRNA) and messenger RNA (mRNA). These amine groups
are the nucleic acid binding moieties, and upon electrostatic interaction, condense these carriers into smaller transportable units,
termed lipoplexes for lipid-based complexes, or polyplexes for
polymer-based complexes [2, 3]. Due to the small or nano-size of
these complexes (including the inorganic nanoparticles), we shall
refer to all such complexes as nanocomplexes.
Polymers such as dendrimers [4, 5], chitosan [6, 7], poly-Llysine (PLL) [7, 8], and polyethyleneimine (PEI) [9, 10] have
gained much interest due to their ability to bind and condense
DNA and have hence been a popular choice for cationic functionalization of inorganic nanoparticles [11]. Hence, these interactions
are mostly ionic in nature. Nanocomplexes can be dynamic in
nature, and depending on the formulation conditions different
conformations may arise. This chapter looks mostly at electrostatic
formulations, with one of the first simplistic models of this type
described by Felgner and Ringold in 1989 for the interaction of
cationic liposomes with plasmid DNA [12], where a single plasmid
is trapped within four liposomes. However, considering the different isoforms especially the supercoiled forms of the DNA, likely
structures that can occur are those resembling the nanoparticles
clustered like grapes around a more branched DNA molecule [13],
or a “bead on a string” conformation [14], or a “spaghetti-meatball” type appearance [15]. In all cases, the cationic nanoparticles
will continually bind to the DNA until a critical point (optimal
binding ratio) is attained.
In the case of inorganic and metal nanoparticles, depending on
the type of synthesis, they can adopt various shapes, such as rods,
spheres, diamonds, stars, cubes, and triangles among others. Cellular uptake can be dependent on shape due to differences in the
particle curvature, which ultimately influences the particle contact
area with the cell membrane [16, 17]. While most studies have
indicated that spherical nanoparticles have a higher propensity to be
internalized in vitro in epithelial cells compared to rod-shaped
particles of similar dimensions [18, 19], a contrasting study has
shown that rod-shaped nanoparticles are more readily taken up by
intestinal epithelial cells, in vitro, than spherical nanoparticles
[17]. However, these two conformations seem most favorable
and hence popular as nanodelivery vehicles. Hence, it is crucial to
fully examine these formulations and their optimal binding prior to
use in vitro or in vivo.
44
Moganavelli Singh