be advantageous over solely solid NPs [124]. These NPs can be synthesized
through well-established procedures to produce particles within a narrow size range
and nearly uniform composition. More information regarding silica synthesis,
parameters control and characterization methods can be found in the literature [121,
125, 126].
Kumar et al. [127] designed SSiNPs conjugated with a near-infrared fluorophore
(DY776) and
124 I for PET and optical imaging in vivo. The injected NPs showed
high sequestration in the spleen (*58%ID/g within 5 min p.i., increasing to 61%
ID/g at 24 h), liver (46%ID/g), lungs (from 9.6% to 4.7%ID/g) and kidney (1.93–
1.22%ID/g at 24 h p.i.). The clearance studies of the injected NPs indicated that
almost all (100%) of the NPs were eliminated via the hepatobiliary pathway by day
15, without any sign of toxicity [127]. Tang et al. [128] reported a simple method to
synthesize monodisperse and size-controlled SiNPs for dual modality lymph node
imaging. The group showed that when the size of conjugates is as small as 20 nm
(ultra-small silica NPs [USSiNPs]), they are rapidly taken by lymph nodes in vivo
and investigations of the lymphatic trafficking were carried out using
64 Cu-labeled
NPs for PET/CT imaging in normal C57BL/6 mice. In the PET/CT images, it is
possible to clearly visualize the left popliteal lymph nodes (P-LN) in as early as
12 min p.i..The signal increased rapidly in the left P-LN from 3.5 to 9.8%ID/g at 12
and 62 min p.i. respectively, indicating efficient lymphatic draining of the NPs. The
group further demonstrated that the SiNPs could be actively targeted to the lymphatic metastases by being conjugated with a DNA aptamer (AS1411), validating
the potential role of SiNPs in the noninvasive tumor staging field [128].
Further improvement in the morphology of SiNPs was achieved by designing
hollow MSNs (HMSNs) with a large interstitial cavity and a mesoporous shell [16].
Chen et al. [129], reported the in vivo tumor-targeted PET/NIR fluorescence (NIRF)
dual-modality imaging and enhanced drug delivery of HMSNs. As-synthesized
HMSNs could load up to 1129.2 mg doxorubicin per gram of HMSN, which was 3–
15 times higher previously reported for MSNs. The NPs were radiolabeled with
64 Cu
using NOTA as a chelator, conjugated with NIR fluorophore ZW800, PEGylated and
further conjugated with TRC105, a chimeric monoclonal antibody against CD105,
for targeted delivery to CD105 overexpressed on tumor vasculature. Through PET
imaging of 4T1 tumor-bearing mice injected with
64 Cu-HMSN-ZW800-TRC105,
rapid and high tumor accumulation (8.5 ± 1.1%ID/g at 0.5 h p.i.) was observed that
peaked at 9.9 ± 0.9%ID/g at 4 h p.i., demonstrating enhanced specific tumor
accumulation (Fig. 2.6a) [129]. In contrast, the tumor uptake in mice injected with
untargeted tracer (
64 Cu-HMSN-ZW800) was found to be only one third of the tracer
containing TRC105 (Fig. 2.6b) at all the time points examined, suggesting that
well-chosen targeting ligands could indeed enhance tumor accumulation of NPs.
These data were further confirmed by blocking studies results (Fig. 2.6c) [129].
Schaffer et al. [130] validated the ability of SiNPs to be intrinsically radiolabeled
to a vast array of radioisotopes (
89 Zr,
68 Ga,
111 In,
90 Y,
177 Lu,
64 Cu), at pH = 7.3,
70 °C and incubation times of up to 1 h. Labeling yields of more than 99% could
be obtained, with the labeling characteristics and stability of the binding depending
on the oxophilicity and hardness of the radioisotope, respectively [130]. However,
28
C. A. Ferreira et al.
through well-established procedures to produce particles within a narrow size range
and nearly uniform composition. More information regarding silica synthesis,
parameters control and characterization methods can be found in the literature [121,
125, 126].
Kumar et al. [127] designed SSiNPs conjugated with a near-infrared fluorophore
(DY776) and
124 I for PET and optical imaging in vivo. The injected NPs showed
high sequestration in the spleen (*58%ID/g within 5 min p.i., increasing to 61%
ID/g at 24 h), liver (46%ID/g), lungs (from 9.6% to 4.7%ID/g) and kidney (1.93–
1.22%ID/g at 24 h p.i.). The clearance studies of the injected NPs indicated that
almost all (100%) of the NPs were eliminated via the hepatobiliary pathway by day
15, without any sign of toxicity [127]. Tang et al. [128] reported a simple method to
synthesize monodisperse and size-controlled SiNPs for dual modality lymph node
imaging. The group showed that when the size of conjugates is as small as 20 nm
(ultra-small silica NPs [USSiNPs]), they are rapidly taken by lymph nodes in vivo
and investigations of the lymphatic trafficking were carried out using
64 Cu-labeled
NPs for PET/CT imaging in normal C57BL/6 mice. In the PET/CT images, it is
possible to clearly visualize the left popliteal lymph nodes (P-LN) in as early as
12 min p.i..The signal increased rapidly in the left P-LN from 3.5 to 9.8%ID/g at 12
and 62 min p.i. respectively, indicating efficient lymphatic draining of the NPs. The
group further demonstrated that the SiNPs could be actively targeted to the lymphatic metastases by being conjugated with a DNA aptamer (AS1411), validating
the potential role of SiNPs in the noninvasive tumor staging field [128].
Further improvement in the morphology of SiNPs was achieved by designing
hollow MSNs (HMSNs) with a large interstitial cavity and a mesoporous shell [16].
Chen et al. [129], reported the in vivo tumor-targeted PET/NIR fluorescence (NIRF)
dual-modality imaging and enhanced drug delivery of HMSNs. As-synthesized
HMSNs could load up to 1129.2 mg doxorubicin per gram of HMSN, which was 3–
15 times higher previously reported for MSNs. The NPs were radiolabeled with
64 Cu
using NOTA as a chelator, conjugated with NIR fluorophore ZW800, PEGylated and
further conjugated with TRC105, a chimeric monoclonal antibody against CD105,
for targeted delivery to CD105 overexpressed on tumor vasculature. Through PET
imaging of 4T1 tumor-bearing mice injected with
64 Cu-HMSN-ZW800-TRC105,
rapid and high tumor accumulation (8.5 ± 1.1%ID/g at 0.5 h p.i.) was observed that
peaked at 9.9 ± 0.9%ID/g at 4 h p.i., demonstrating enhanced specific tumor
accumulation (Fig. 2.6a) [129]. In contrast, the tumor uptake in mice injected with
untargeted tracer (
64 Cu-HMSN-ZW800) was found to be only one third of the tracer
containing TRC105 (Fig. 2.6b) at all the time points examined, suggesting that
well-chosen targeting ligands could indeed enhance tumor accumulation of NPs.
These data were further confirmed by blocking studies results (Fig. 2.6c) [129].
Schaffer et al. [130] validated the ability of SiNPs to be intrinsically radiolabeled
to a vast array of radioisotopes (
89 Zr,
68 Ga,
111 In,
90 Y,
177 Lu,
64 Cu), at pH = 7.3,
70 °C and incubation times of up to 1 h. Labeling yields of more than 99% could
be obtained, with the labeling characteristics and stability of the binding depending
on the oxophilicity and hardness of the radioisotope, respectively [130]. However,
28
C. A. Ferreira et al.