adenocarcinoma – the fluorescence signals lasted >96 h post-systemic injection
(Fig. 10c) [89]. In the next study, they further modified these nanoparticles with
active targeting moieties of human holotransferrin, anti-CD71 antibody, and short
gastrin peptides. They validated the systemic in vivo targeting to breast and pancreatic cancer lesions, respectively [92].
Elemental silicon itself is an endogenous substance, and it has been used extensively to fabricate (porous) silica nanostructures with a well-defined size and morphology via simple sol-gel synthesis [61]. Fluorescent dye molecules can be
physically entrapped into the porous nano-channels of silica matrix [93]. The fluorescence remained unquenched up to very high concentrations of dye molecules. In
2011, Igor Sokolov and coworkers described small silica particles (ranging from
20 to 50 nm) with a high dye loading capacity (0.8–9.3 mg rhodamin6G (R6G dye)
per g particles) using several organotriethoxysilanes (MTMS, ETES, or PTES) for
the co-precursors of silica. They found the relative brightness from the fluorescent
dye-doped silica particles has 30–770 times a QY that is higher than non-dimerized
R6G dye molecules and 1.5–39 times of CdSe/ZnS QDs [94]. Importantly, some
fluorescent silica nanoparticles (e.g., Cornell dots; core-shell type of dye-rich core
surrounded by denser silica network [95]) have exceptional biocompatibility and
were approved for the first human clinical trials for cancer diagnosis [96]. These 6–7nm-sized Cornell dots (containing the dye, Cy5) attached with cyclic arginineglycine-aspartic acid (cRGDY) peptides that target integrin α v β 3 and
124 I radiotracer
for positron emission tomography (PET) imaging have been administered to five
patients with metastatic melanoma [97]. Their favorable PK/biodistribution profiles
and safety assessment showed the potential for clinical translation of these cancertargeted, renally excreted inorganic nanoparticles. In addition to the visible light
dyes (R6G, Cy5, FITC), NIR-emitting ICG dyes have also been encapsulated to the
nanostructures of dense silica [98], mesoporous silica [99, 100], and porous silicon
[101] and successfully utilized as for NIR optical imaging as well as for
photoacoustic imaging in recent years.
7 Conclusion
Innovative nanotechnology has enabled the development of several new inorganic
fluorescent nanomaterials to realize sensitive, high-resolution, optical imaging. QDs
have been extensively investigated to overcome the limitations of organic fluorescent dyes with its superior photo-physical properties such as size-tunable
photoluminescence, narrow emission, and low photo-bleaching. Chemical modifications with additional organic layers (e.g., PEG, targeting ligands) on QD surfaces
can improve the blood circulation and diffusion of QD for sentinel lymph node
(SLN) mapping, vasculature imaging, or more complex targeted imaging of tumor
cells in vivo. Subsequently, further research has focused more on NIR-emitting QDs
(NIR-I or NIR-II) (e.g., core/shell CdSe/CdTe QDs, Ag 2 S QDs) to improve the
imaging sensitivity of the conventional, visible luminescent QDs.
Inorganic Fluorescent Nanomaterials
73
(Fig. 10c) [89]. In the next study, they further modified these nanoparticles with
active targeting moieties of human holotransferrin, anti-CD71 antibody, and short
gastrin peptides. They validated the systemic in vivo targeting to breast and pancreatic cancer lesions, respectively [92].
Elemental silicon itself is an endogenous substance, and it has been used extensively to fabricate (porous) silica nanostructures with a well-defined size and morphology via simple sol-gel synthesis [61]. Fluorescent dye molecules can be
physically entrapped into the porous nano-channels of silica matrix [93]. The fluorescence remained unquenched up to very high concentrations of dye molecules. In
2011, Igor Sokolov and coworkers described small silica particles (ranging from
20 to 50 nm) with a high dye loading capacity (0.8–9.3 mg rhodamin6G (R6G dye)
per g particles) using several organotriethoxysilanes (MTMS, ETES, or PTES) for
the co-precursors of silica. They found the relative brightness from the fluorescent
dye-doped silica particles has 30–770 times a QY that is higher than non-dimerized
R6G dye molecules and 1.5–39 times of CdSe/ZnS QDs [94]. Importantly, some
fluorescent silica nanoparticles (e.g., Cornell dots; core-shell type of dye-rich core
surrounded by denser silica network [95]) have exceptional biocompatibility and
were approved for the first human clinical trials for cancer diagnosis [96]. These 6–7nm-sized Cornell dots (containing the dye, Cy5) attached with cyclic arginineglycine-aspartic acid (cRGDY) peptides that target integrin α v β 3 and
124 I radiotracer
for positron emission tomography (PET) imaging have been administered to five
patients with metastatic melanoma [97]. Their favorable PK/biodistribution profiles
and safety assessment showed the potential for clinical translation of these cancertargeted, renally excreted inorganic nanoparticles. In addition to the visible light
dyes (R6G, Cy5, FITC), NIR-emitting ICG dyes have also been encapsulated to the
nanostructures of dense silica [98], mesoporous silica [99, 100], and porous silicon
[101] and successfully utilized as for NIR optical imaging as well as for
photoacoustic imaging in recent years.
7 Conclusion
Innovative nanotechnology has enabled the development of several new inorganic
fluorescent nanomaterials to realize sensitive, high-resolution, optical imaging. QDs
have been extensively investigated to overcome the limitations of organic fluorescent dyes with its superior photo-physical properties such as size-tunable
photoluminescence, narrow emission, and low photo-bleaching. Chemical modifications with additional organic layers (e.g., PEG, targeting ligands) on QD surfaces
can improve the blood circulation and diffusion of QD for sentinel lymph node
(SLN) mapping, vasculature imaging, or more complex targeted imaging of tumor
cells in vivo. Subsequently, further research has focused more on NIR-emitting QDs
(NIR-I or NIR-II) (e.g., core/shell CdSe/CdTe QDs, Ag 2 S QDs) to improve the
imaging sensitivity of the conventional, visible luminescent QDs.
Inorganic Fluorescent Nanomaterials
73