Asian Journal of Pharmacodynamics and Pharmacokinetics

Cheng TF et al. Asian Journal of Pharmacodynamics and Pharmacokinetics 2009; 9(1):27-49
while the non-phagocytosed particles were found
entering into alveolar epithelial in day 1 after
exposure. Several inflammatory reactions including
inflammatory and immune cells increase, clinical
pathological changes: follicular hyperplasia, protein
effusion, pulmonary capillary vessel hyperaemia
and alveolar lipoproteinosis in lung were observed.
The sustain burden of particles in AM and
epithelium cells has caused lung emphysema and
pro-sign of lung fibrosis. At the post-instilled day
30, the typical coagulation parameters, prothrombin
time (PT) and activated partial thromboplastin time
(APTT) in blood of low dose 22 nm-Fe 2 O 3 treated
rats were significantly longer than the controls. We
concluded that both of the two-sized Fe 2 O 3 particle
intratracheal exposure could induce lung injury.
Comparing with the submicron-sized Fe 2 O 3 particle,
the nano-sized Fe 2 O 3 particle may increase
microvascular permeability and cell lysis in lung
epitheliums and disturb blood coagulation
parameters significantly. [18]
Superparamagnetic iron oxide nanoparticles
(SPIONs) are applied in stem cell labeling because
of their high magnetic susceptibility as compared
with ordinary paramagnetic species, their low
toxicity, and their ease of magnetic manipulation.
The present work is the study of CD133+ stem cell
labeling by SPIONs coupled to a specific antibody
(AC133), resulting in the antigenic labeling of the
CD133+ stem cell, and a method was developed for
the quantification of the SPION content per cell,
necessary for molecular imaging optimization. Flow
cytometry analysis established the efficiency of the
selection process and helped determine that the
CD133 cells selected by chromatographic affinity
express the transmembrane glycoprotein CD133.
The presence of antibodies coupled to the SPION,
expressed in the cell membrane, was observed by
transmission electron microscopy. Quantification of
the SPION concentration in the marked cells using
the ferromagnetic resonance technique resulted in a
value of 1.70 × 10–13 mol iron (9.5 pg) or 7.0 × 10 6
nanoparticles per cell (the measurement was carried
out in a volume of 2 µL containing about 6.16 × 10 5
pg iron, equivalent to 4.5 × 10 11 SPIONs). [19]
Mechanisms of development of protein
misfolding diseases
Misfolding and self-assembly of proteins in
nanoaggregates of different sizes and morphologies
(nanoensembles, primarily nanofilaments and
nanorings) is a complex phenomenon that can be
facilitated, impeded, or prevented by interactions
with various intracellular metabolites, intracellular
nanomachines controlling protein folding, and
interactions with other proteins. A fundamental
understanding of molecular processes leading to
misfolding and self-aggregation of proteins
involved in various neurodegenerative diseases will
provide important information to help identify
appropriate therapeutic routes to control these
processes. An elevated propensity of misfolded
protein conformation in solution to aggregate with
the formation of various morphologies impedes the
use of traditional physiochemical approaches for
studies of misfolded conformations of proteins.
Kransnoslobodtsev et al tethered the protein
molecules to surfaces to prevent aggregation and,
with force spectroscopy using an atomic force
microscopy, probed the interaction between protein
molecules depending on their conformations.
Research results show that formation of filamentous
aggregates is facilitated at pH values corresponding
to the maximum of rupture forces. They report here
on development of a novel surface chemistry for
anchoring of amyloid β (Aβ) peptides at their
N-terminal moieties. The use of the site-specific
immobilization procedure allowed us to measure the
rupture of Aβ-Aβ contacts at the single-molecule
level. The rupture of these contacts is accompanied
by the extension of the peptide chain detected by a
characteristic elastomechanical component of the
force-distance curves. Potential applications of
nanomechanical studies for understanding the
mechanisms of development of protein misfolding
diseases are discussed. [20]
Research and Application of Carbon
Nanotubes
A good representative of this fast-moving field
is the family of nanomaterials known as carbon
nanotubes (CNTs). These all-carbon tubes are just a
few nanometers in diameter, which makes them
comparable in girth to DNA molecules, and come in
either singlewalled varieties or multiwalled varieties
with a nesting of carbon shells resembling the
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