Biomedical Engineering Reference
In-Depth Information
tissue (Larson et al.
2003
). Comparison of QDs to fl uorescein isothiocyanate-
conjugated dextran imaged at the same depth showed that QD probes were brighter
and hence revealed greater detail. Near-infrared QDs have been injected intradermally
in a pig and imaged real-time with virtually no autofl uorescence of the tissue (Kim
et al.
2004
). This technique has allowed surgeons to follow the migration of the QDs
towards the sentinel lymph node (SLN) and identify the position of the SLN quickly,
providing visualization and mapping during surgical procedures, thus eliminating the
need for both the radioactive tracers (Kim et al.
2004
) .
The BBB tightly regulates the passage of selected molecules into the brain paren-
chyma and thus limits the accessibility of biomolecules to the brain presenting a
challenge for the in vivo delivery of imaging agents and compounds to the brain.
Accumulating evidence in the past 2 decades has shown, however, that proteins and
peptides are capable of crossing the BBB via specifi c transport systems such as
receptor and carrier-mediated endothelial cell transport systems (Pan and Kastin
2004
; Costantino et al.
2005
; Olivier
2005
). Recent work using polymeric nanopar-
ticles (10-100 nm) with surface-conjugated antibodies and other peptides has shown
success in crossing the BBB (Roney et al.
2005
). Although QD delivery to the brain
has yet to be investigated, the small size of QDs as well as their ease of conjugation
to a variety of compounds makes them promising candidates for similar passage
across the BBB. Their property of fl uorescence eliminates the need for conjugation
with a dye molecule as in the case of polymeric nanoparticles and thus QDs can
serve as probes for labeling of neural targets in live brain tissue as well as multi-
effector platforms for drug transport across the BBB.
Nanoparticles have been delivered into the eye with greater ease than the brain
due to better accessibility and may prove to be a feasible fi rst step to imaging intact
neural tissue as well as for further development of nanoparticle therapies. In their
study, de Kozak et al. injected fl uorescent Poly (methoxypolyethyleneglycol cyano-
acrylate-co-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles into the vitre-
ous of rats with experimental autoimmune uveoretinitis and found that the
nanoparticles dispersed freely in the anterior and posterior sections of the eye and
infi ltrated the retina through the end feet of glial cells (de Kozak et al.
2004
) . When
the nanoparticles were loaded with tamoxifen, the disease severity was inhibited
indicating the effectiveness of the intraocular treatment. Bourges et al. showed that
polymer nanoparticles injected into the vitreous were mobile, entering the retina
and retinal epithelium, while maintaining anatomical integrity of the tissue (Bourges
et al.
2003
) .
10
Conclusions and Future Directions
QD-based biological applications have emerged only in the past few years; however,
the rapid success of QDs for imaging cells and tissue in a variety of cellular systems
and imaging modalities indicates the versatility and potential of this nanotechnology
to contribute to biomedicine. In the realm of neuroscience, the initial studies
