Quantum-sized, porous silicon nanoparticles prepared by electrochemical etching
of silicon wafer have subsequent luminescence arising in the 600–1,000 nm range
from a combination of a quantum confinement effect and surface defect localized at
the Si-SiO 2 interface [59]. Porous silicon has become one of the most powerful
nanomaterials for optical in vivo imaging with respect to its adaptability, biodegradability, and capability for background-free imaging. Porous silicon nanoparticles are
highly adaptable to load large volumes of various drugs (e.g., small molecules,
nucleic acid, protein drugs) or additional imaging agents (e.g., Gd complex, magnetic particles) within their size-tunable pores [60]. Porous silicon nanoparticles can
biodegrade into benign orthosilicic acid (Si(OH) 4 ; the element silicon itself is an
endogenous substance (Fig. 6a) followed by excretion as urine [57]. The intravenously administered porous silicon nanoparticles were completely degraded in
4 weeks without any measurable in vivo toxicity over 1–12 months (Fig. 6b, c). In
addition, porous silicon nanoparticles enable autofluorescence-free and time-gated
fluorescence (TGF) imaging of tissue in vivo because they can provide the unusual
long emission lifetime (5–13 ms) compared to nanosecond lifetimes of typical
fluorescent organic molecules or QDs [58]. Thus, in time-gated fluorescence
(TGF) imaging (images are captured at a delayed time after excitation), the signal
could be effectively eliminated from the shorter-lived emission signals.
Figure 6d shows a nude mouse injected subcutaneously with PEGylated luminescent porous silicon nanoparticles (PEG-LPSiNPs). Here, the TGF imaging
revealed intensive signals in the PEG-LPSiNP injection (T1) with negligible signals
from the Cy3.5 injection (T2) or from the background tissue autofluorescence (T3).
The fluorescent signals appeared in all three spots under the continuous-wave
(CW) imaging (steady-state conditions; no time gating). Therefore, as an alternative
to cytotoxic QDs, there has been much progress in the use of porous silicon
nanoparticles for multimodal bio-imaging [61] and targeted therapy [62]. However,
considerable future research still remains to overcome the limitations of luminescent
porous silicon nanoparticles such as low quantum yield and difficulty in sizecontrolled mass production.
Gold nanoparticles (10–100 nm in size) are an efficient light scattering and
absorbing center known to generate visible luminescence and heat upon excitation
at λ SPR based on its surface resonant oscillation of electrons [63]. In contrast, gold
nanoclusters (AuNCs) consisting of several tens of atoms (<2 nm in size) have
molecular-like, discrete electronic states due to the spatial confinement of free
electrons [64]. Therefore, gold nanoclusters can feature all unique optical properties
that semiconductor QDs have. In the past decade, there have been many investigations of synthetic methods for fine control of the number of gold atoms in a cluster.
Generally, gold nanoclusters (AuNCs) are synthesized by the chemical reduction
of gold precursors in the presence of strong stabilizer. Owing to a strong affinity of
thiols to the Au surface, thiol-containing small molecules (e.g., glutathione [66, 67],
dodecanethiol [68]) have been extensively used as a stabilizing template for gold
clusters [69]. As a simple, green synthetic route, macromolecules (e.g., protein [70],
DNA [71], dendrimer [64]) have also been also employed as a surface template to
direct the formation of Au clusters with a substantial quantum yield (e.g., bovine
64
T. Kim and J. V. Jokerst
of silicon wafer have subsequent luminescence arising in the 600–1,000 nm range
from a combination of a quantum confinement effect and surface defect localized at
the Si-SiO 2 interface [59]. Porous silicon has become one of the most powerful
nanomaterials for optical in vivo imaging with respect to its adaptability, biodegradability, and capability for background-free imaging. Porous silicon nanoparticles are
highly adaptable to load large volumes of various drugs (e.g., small molecules,
nucleic acid, protein drugs) or additional imaging agents (e.g., Gd complex, magnetic particles) within their size-tunable pores [60]. Porous silicon nanoparticles can
biodegrade into benign orthosilicic acid (Si(OH) 4 ; the element silicon itself is an
endogenous substance (Fig. 6a) followed by excretion as urine [57]. The intravenously administered porous silicon nanoparticles were completely degraded in
4 weeks without any measurable in vivo toxicity over 1–12 months (Fig. 6b, c). In
addition, porous silicon nanoparticles enable autofluorescence-free and time-gated
fluorescence (TGF) imaging of tissue in vivo because they can provide the unusual
long emission lifetime (5–13 ms) compared to nanosecond lifetimes of typical
fluorescent organic molecules or QDs [58]. Thus, in time-gated fluorescence
(TGF) imaging (images are captured at a delayed time after excitation), the signal
could be effectively eliminated from the shorter-lived emission signals.
Figure 6d shows a nude mouse injected subcutaneously with PEGylated luminescent porous silicon nanoparticles (PEG-LPSiNPs). Here, the TGF imaging
revealed intensive signals in the PEG-LPSiNP injection (T1) with negligible signals
from the Cy3.5 injection (T2) or from the background tissue autofluorescence (T3).
The fluorescent signals appeared in all three spots under the continuous-wave
(CW) imaging (steady-state conditions; no time gating). Therefore, as an alternative
to cytotoxic QDs, there has been much progress in the use of porous silicon
nanoparticles for multimodal bio-imaging [61] and targeted therapy [62]. However,
considerable future research still remains to overcome the limitations of luminescent
porous silicon nanoparticles such as low quantum yield and difficulty in sizecontrolled mass production.
Gold nanoparticles (10–100 nm in size) are an efficient light scattering and
absorbing center known to generate visible luminescence and heat upon excitation
at λ SPR based on its surface resonant oscillation of electrons [63]. In contrast, gold
nanoclusters (AuNCs) consisting of several tens of atoms (<2 nm in size) have
molecular-like, discrete electronic states due to the spatial confinement of free
electrons [64]. Therefore, gold nanoclusters can feature all unique optical properties
that semiconductor QDs have. In the past decade, there have been many investigations of synthetic methods for fine control of the number of gold atoms in a cluster.
Generally, gold nanoclusters (AuNCs) are synthesized by the chemical reduction
of gold precursors in the presence of strong stabilizer. Owing to a strong affinity of
thiols to the Au surface, thiol-containing small molecules (e.g., glutathione [66, 67],
dodecanethiol [68]) have been extensively used as a stabilizing template for gold
clusters [69]. As a simple, green synthetic route, macromolecules (e.g., protein [70],
DNA [71], dendrimer [64]) have also been also employed as a surface template to
direct the formation of Au clusters with a substantial quantum yield (e.g., bovine
64
T. Kim and J. V. Jokerst