an uptake value of 4.5 ± 0.6%ID/g at 0.5 h p.i that peaked at 6 h p.i. (11.4 ± 2.1%
ID/g) and remained in the tumor tissue for up to 48 h p.i. In contrast, the NP tumor
uptake based solely on the EPR effect (passive targeting) was approximately three
times lower (peaking at 3.6 ± 0.3%ID/g) [21]. Further review on nonporous silica
NPs [132], USSiNPs [122] and HMSNs [133] for nanomedicine application can be
found elsewhere.
2.6 Other Nanomaterials
2.6.1 Carbon Nanotubes
Carbon nanotubes (CNTs) are hollow-structured nanomaterials made of graphite
arranged and ordered in a very precise manner, conferring them with a variety of
properties such as ultra-light weight and high aspect ratio. Every carbon atom on
the NP surface can serve as a conjugation site for a range of ligands, which can be
explored for multifunctionalized biological applications [134]. For that, these
nanomaterials, ranging between 1 nm-1 µm, have been employed as optical
imaging probes, therapeutic agents and drug nanocarriers [135]. Furthermore, the
strong absorption in NIR and far NIR (NIR II) windows (750–1000 and 1000–
1700 nm, respectively), allows deep tissue imaging with high resolution, enhanced
contrast and minimized autofluorescence and photobleaching, leading to widespread applications in optical and photoacoustic imaging, photothermal imaging
and therapy [16]. In addition, CNTs are suitable Raman probes for biological
sensing and imaging, owing to their extremely large scattering cross-sections,
allowing strong resonance Raman scattering [136]. Wang et al. [137] were the first
use a radioisotope (
125 I) to investigate the biodistribution of CNTs in vivo. Since
then, CNTs has been radiolabeled with several radioisotopes such as
14
C [138],
111 In [139],
99m Tc [140],
86 Y [141] and
64 Cu [142]. For example, Liu et al. [142]
developed
64 Cu-DOTA-labeled single-wall carbon nanotubes (
64 Cu-DOTASWNTs) functionalized with PEG and cRGDyk peptide. Results indicated a
longer blood circulation, superior hydrophilicity and reduced RES uptake when
compared with previously reported studies [143]. Conjugation with the peptide
conferred integrin a v b 3 specific uptake in U87MG glioblastoma xenografts (*13%
ID/g) (Fig. 2.7a), attributed to the multivalency effect of SWNTs, which was further
confirmed by the unique Raman signatures of the nanoprobes [142]. Chelator-free
radiolabeling has also been reported, in which alpha-emitters (
225 Ac
3+ ) [144] and
positron-emitters (
64
Cu
2+ ) [145] were loaded and confined inside the carbon nanotubes by simple sonication. This radiolabeling method could have the advantage of
preventing radioisotope translocation and leakage, by protecting the radioisotopes
from transmetallation, and consequent off-target toxicity in vivo. Despite the fact
that several groups reported the use of radiolabeled CNTs, the progress in
CNT-based probes for nuclear imaging has relatively slowed down in the last few
30
C. A. Ferreira et al.
ID/g) and remained in the tumor tissue for up to 48 h p.i. In contrast, the NP tumor
uptake based solely on the EPR effect (passive targeting) was approximately three
times lower (peaking at 3.6 ± 0.3%ID/g) [21]. Further review on nonporous silica
NPs [132], USSiNPs [122] and HMSNs [133] for nanomedicine application can be
found elsewhere.
2.6 Other Nanomaterials
2.6.1 Carbon Nanotubes
Carbon nanotubes (CNTs) are hollow-structured nanomaterials made of graphite
arranged and ordered in a very precise manner, conferring them with a variety of
properties such as ultra-light weight and high aspect ratio. Every carbon atom on
the NP surface can serve as a conjugation site for a range of ligands, which can be
explored for multifunctionalized biological applications [134]. For that, these
nanomaterials, ranging between 1 nm-1 µm, have been employed as optical
imaging probes, therapeutic agents and drug nanocarriers [135]. Furthermore, the
strong absorption in NIR and far NIR (NIR II) windows (750–1000 and 1000–
1700 nm, respectively), allows deep tissue imaging with high resolution, enhanced
contrast and minimized autofluorescence and photobleaching, leading to widespread applications in optical and photoacoustic imaging, photothermal imaging
and therapy [16]. In addition, CNTs are suitable Raman probes for biological
sensing and imaging, owing to their extremely large scattering cross-sections,
allowing strong resonance Raman scattering [136]. Wang et al. [137] were the first
use a radioisotope (
125 I) to investigate the biodistribution of CNTs in vivo. Since
then, CNTs has been radiolabeled with several radioisotopes such as
14
C [138],
111 In [139],
99m Tc [140],
86 Y [141] and
64 Cu [142]. For example, Liu et al. [142]
developed
64 Cu-DOTA-labeled single-wall carbon nanotubes (
64 Cu-DOTASWNTs) functionalized with PEG and cRGDyk peptide. Results indicated a
longer blood circulation, superior hydrophilicity and reduced RES uptake when
compared with previously reported studies [143]. Conjugation with the peptide
conferred integrin a v b 3 specific uptake in U87MG glioblastoma xenografts (*13%
ID/g) (Fig. 2.7a), attributed to the multivalency effect of SWNTs, which was further
confirmed by the unique Raman signatures of the nanoprobes [142]. Chelator-free
radiolabeling has also been reported, in which alpha-emitters (
225 Ac
3+ ) [144] and
positron-emitters (
64
Cu
2+ ) [145] were loaded and confined inside the carbon nanotubes by simple sonication. This radiolabeling method could have the advantage of
preventing radioisotope translocation and leakage, by protecting the radioisotopes
from transmetallation, and consequent off-target toxicity in vivo. Despite the fact
that several groups reported the use of radiolabeled CNTs, the progress in
CNT-based probes for nuclear imaging has relatively slowed down in the last few
30
C. A. Ferreira et al.