Biomedical Engineering Reference
In-Depth Information
greater density than the conventional CT/DNA. Analysis using small angle X-ray
scattering (SAXS) indicated that incorporating
g
-PGA caused the formation of
compounded nanoparticles whose internal structure might facilitate the dissociation
of CT and DNA. As compared with CT/DNA,
g
-PGA/CT/DNA nanoparticles
improved their penetration depth into mouse skin and enhanced gene expression.
Moreover, in addition to improving the release of DNA intracellularly, the
incorporation of
g
-PGA in nanoparticles markedly increased their cellular internal-
ization [
131
]. Taken together, the results show that
g
-PGA significantly enhanced
the transfection efficiency of this developed gene delivery system. The results
indicated that
g
-PGA played multiple important roles in enhancing the cellular
uptake and transfection efficiency of
g
-PGA/CT/DNA nanoparticles. This delivery
system may be useful for DNA vaccine development.
Kurosaki et al. also developed a vector coated by
g
-PGA for effective and safe
gene delivery [
132
]. To develop a useful nonviral vector, PIC constructed with
pDNA, PEI, and various polyanions, such as polyadenylic acid, polyinosinic-po-
lycytidylic acid,
a
-polyaspartic acid, and
g
-PGA were prepared. The pDNA/PEI
complex had a strong cationic surface charge and showed extremely high trans-
gene efficiency although it agglutinated with erythrocytes and had extremely high
cytotoxicity. The
g
-PGA could electrostatically coat the pDNA/PEI complex to
form stable anionic particles. The coating of
g
-PGA dramatically decreased the
toxicities of pDNA/PEI complex. Moreover, the pDNA/PEI/
g
-PGA complex was
highlytakenupbythecellsviaa
g
-PGA-specific receptor-mediated pathway and
showed extremely high transgene efficiencies. Further studies are necessary to
examine the detailed uptake mechanism and clinical safety as gene delivery
vector.
4 Control of Intracellular Distribution of Nanoparticles
4.1
pH-Responsive Nanoparticles
In general, particulate materials can be easily internalized into the cells via endo-
cytosis, depending on their size, shape, and surface charge. However, the
internalized materials are mostly trafficked from acidic endosomes to lysosomes,
where degradation may occur. Thus, degraded exogenous antigens are presented by
the MHC class II presentation pathway, and a part of the pathway involves
antibody-mediated immune responses. In contrast, antigens within the cytosol are
processed into proteasomes and presented by the MHC class I pathway, a pathway
involved in the cytotoxic T-lymphocyte (CTL) response [
99
-
101
]. Therefore, the
induction of antigen-specific cellular immunity by exogenous antigens is needed for
the regulation of intracellular distribution of antigens. The escape of internalized
