One possible strategy is to develop a new class of nanoparticles whose persistent
luminescence can be renewable in vivo through living tissues. In 2014, Scherman
and coworkers synthesized 80 nm Cr
3+ -doped zinc gallium oxide (ZGO)
nanoparticles and observed whether the persistent luminescence can be activated
in situ whenever required with no time limit [88]. The particles have several
excitation peaks with one within the tissue transparency window (rectangle with
hatching) (Fig. 9a) resulting in a NIR ¼ persistent luminescence by a low-powered,
orange/red light-emitting diode (LED) illumination (Fig. 9b). Simple illumination
through living tissues with visible light was sufficient to activate persistent luminescence of ZGO-OH nanoparticles – intense signals were shown from the reticuloendothelial system (RES) organs (e.g., liver) within the deep tissues (Fig. 9c). As for
the applications, the authors assessed the ability of as-prepared nanoparticles for
in vivo imaging for vasculature imaging, tumor detection, and longitudinal cell
tracking in a mouse model. With additional surface coating (amino, carboxy, or
PEG), these nanoparticles become very colloidal stable and long circulating after
intravenous injections; therefore, they successfully showed these persistent luminescent nanoparticles could be used to image the tumors via passive targeting (PEG
coating) (Fig. 9d). Furthermore, the amino-coated probes could label macrophage
cells for visualization in vivo (Fig. 9e). Additionally, the pathway of nanoparticles
could be detected in the gastrointestinal tract after oral administration.
6 Dye-Doped Inorganic Nanoparticles (Calcium Phosphate,
Silica)
Biologically resorbable and optically transparent inorganic materials (e.g., calcium
phosphate, silica) can encapsulate dyes into their well-defined, large-surfaced,
nanoporous structures and are an effective way of enhancing the photostability of
organic fluorophores. These dye-doped nanoparticles can minimize their fluorescence quenching or enzymatic degradation. However, to achieve high sensitivity and
specificity of the fluorescence signals, it is critically important to select appropriate
dye molecules and increase the loading capacity with no change in particle size and
morphology.
Calcium phosphate is found in endogenous biominerals including bone and teeth.
It can easily form colloidally stable nanoparticles by reverse microemulsion synthesis [90]. In the first such study, Adir et al. successfully synthesized and investigated
the potentials of NIR-emitting calcium phosphate nanoparticles (CPNPs) by
entrapping indocyanine green (ICG) [91]. In this study, they prepared the welldispersed, ICG dye-doped CPNP (ICG-CPNP) (Fig. 10a), and found that the
photostability is 500% longer relative to the free dye (Fig. 10b). PEGylated
ICG dye-doped CPNPs exhibited much longer blood circulation than free ICG
(free ICG in physiological environments experience the rapid aggregation
and clearance from the body) and passively accumulated to xenografted breast
70
T. Kim and J. V. Jokerst
luminescence can be renewable in vivo through living tissues. In 2014, Scherman
and coworkers synthesized 80 nm Cr
3+ -doped zinc gallium oxide (ZGO)
nanoparticles and observed whether the persistent luminescence can be activated
in situ whenever required with no time limit [88]. The particles have several
excitation peaks with one within the tissue transparency window (rectangle with
hatching) (Fig. 9a) resulting in a NIR ¼ persistent luminescence by a low-powered,
orange/red light-emitting diode (LED) illumination (Fig. 9b). Simple illumination
through living tissues with visible light was sufficient to activate persistent luminescence of ZGO-OH nanoparticles – intense signals were shown from the reticuloendothelial system (RES) organs (e.g., liver) within the deep tissues (Fig. 9c). As for
the applications, the authors assessed the ability of as-prepared nanoparticles for
in vivo imaging for vasculature imaging, tumor detection, and longitudinal cell
tracking in a mouse model. With additional surface coating (amino, carboxy, or
PEG), these nanoparticles become very colloidal stable and long circulating after
intravenous injections; therefore, they successfully showed these persistent luminescent nanoparticles could be used to image the tumors via passive targeting (PEG
coating) (Fig. 9d). Furthermore, the amino-coated probes could label macrophage
cells for visualization in vivo (Fig. 9e). Additionally, the pathway of nanoparticles
could be detected in the gastrointestinal tract after oral administration.
6 Dye-Doped Inorganic Nanoparticles (Calcium Phosphate,
Silica)
Biologically resorbable and optically transparent inorganic materials (e.g., calcium
phosphate, silica) can encapsulate dyes into their well-defined, large-surfaced,
nanoporous structures and are an effective way of enhancing the photostability of
organic fluorophores. These dye-doped nanoparticles can minimize their fluorescence quenching or enzymatic degradation. However, to achieve high sensitivity and
specificity of the fluorescence signals, it is critically important to select appropriate
dye molecules and increase the loading capacity with no change in particle size and
morphology.
Calcium phosphate is found in endogenous biominerals including bone and teeth.
It can easily form colloidally stable nanoparticles by reverse microemulsion synthesis [90]. In the first such study, Adir et al. successfully synthesized and investigated
the potentials of NIR-emitting calcium phosphate nanoparticles (CPNPs) by
entrapping indocyanine green (ICG) [91]. In this study, they prepared the welldispersed, ICG dye-doped CPNP (ICG-CPNP) (Fig. 10a), and found that the
photostability is 500% longer relative to the free dye (Fig. 10b). PEGylated
ICG dye-doped CPNPs exhibited much longer blood circulation than free ICG
(free ICG in physiological environments experience the rapid aggregation
and clearance from the body) and passively accumulated to xenografted breast
70
T. Kim and J. V. Jokerst