Rational Design of Fluorophores for In Vivo Applications - Progress in Molecular Biology and Translational Science - page 70

aggregation behavior of resulting conjugates depends on the terminal groups
present on the periphery of the dendrons.
Another strategy to improve the water solubility, stability, and optical
properties of cyanines is encapsulation of fluorophore inside the cyclodex-
trin cavity. Complexes of cyclodextrins with pentamethine 87,88 and
heptamethine 89 cyanines have been reported. The complexation
generally reduces the fluorescence quantum yields but substantially
increases photostability up to nine times compared to the uncomplexed
cyanines, both in solution as well as in cells. 87,88 Cyanine-cyclodextrin
complexes have not been examined in vivo yet.
The encapsulation inside the nanostructures has been intensively studied
recently as a method for improving stability as well as photochemical and
pharmacodynamic properties of cyanines. For example, silica nanoparticles
have received considerable attention as potential fluorophore stabilizers and
nanocarriers in vivo because of the nontoxicity of silica and its optical trans-
parency. ICG has been incorporated inside mesoporous silica nanoparticles,
where dye molecules have been entrapped inside nanopores by electro-
static interaction between negatively charged sulfonic groups and tetra-
alkylammonium-modified silica. 90 The resulting fluorescent nanoparticles
with diameters of 50-100 nm are relatively stable under physiological condi-
tions, without substantial fluorophore leakage, and show maximum fluores-
cence at 800 m g of ICG per gram of silica (whereas the maximum fluorescence
of free ICG in solution is achieved at concentration of 2 m g/mL); thus encap-
sulation of ICG allows much brighter fluorescence. In vivo biodistribution of
the resulting nanoparticles has been examined as well. 90 The cyanine fluo-
rophore Dy776 has been also encapsulated inside ultrafine ( < 20 nmdiameter)
organically modified silica nanoparticles, and their in vivo biodistribution has
been examined. 91 The use of organically modified silica as a nanocarrier offers
an additional capability to attach the targeting agent. 91
ICGhas also been encapsulated inside surface-modified calciumphosphate
or calcium phosphosilicate composite nanoparticles. 80,92 phosphate buffered
saline (PBS) suspension of ICG-doped calcium phosphate (average diameter
of 16 nm) nanoparticles showed twofold higher quantum yield of
fluorescence per molecule of ICG and five times longer fluorescence half-
life than a solution of the free fluorophore. Both calcium phosphate and
calcium phosphosilicate nanoparticles with encapsulated ICG have been
used for in vivo cancer imaging. 80,92
The stability, water solubility, blood circulation time, and tumor accumu-
lation of ICG (or its analogs) have also been improved by encapsulation in