The successful sealing and filling by metal halides were confirmed by highresolution TEM and scanning TEM.
The surface of these filled SWNTs was then covalently modified with bi-antennary
D-N-acetylglucosamine (GlcNAc) dendron to further improve the water dispersibility
and the biocompatibility of the nanosystems, and to provide the ability to target lung
tissues. For this, mild azomethine ylid 1,3-dipolar cycloaddition (Prato reaction) [67]
allowed the attachment of PEGylated glycoconjugate appendages together with the
2,3,5-triiodophenyl motif used as tagging agent, with the preservation of the tubular
structure and the closed ends of the filled SWNTs. Considering the fact that iodine
radioemitters used for treatment of thyroid cancer are still considered to be among the
most effective for systemic radiotherapy, the potential of the resulting functionalized
125
I-nanocapsule 28 to act as defined containers capable of localizing radionuclides
was investigated (Fig. 8a). Intravenous administration of 28, in the tail vein
of BALB/c mice was tracked in vivo using single-photon emission computed
tomography (SPECT). Results suggested strong differences in tissue and organ
biodistribution of the filled and glycosylated 28 compared to non-encapsulated
Na
125
I. Particularly, nanoencapsulation of
125
I prevented leakage of the radionuclide
to organs such as the thyroid and the stomach, known to have innate affinity for iodide,
and also avoided urinary or biliary excretion of the iodide, even after 7 days (Fig. 8b, c).
In fact, when 28 was administrated, the tissue distribution profile indicated
predominantly specific lung accumulation and persistent retention of the construct,
while no signals were detected in the thyroid, stomach, or bladder at t ¼ 0 or after
4 h, 24 h, or 7 days. This specificity was rationalized by the authors to be attributed to
the presence of lung-localized proteins able to bind the GlcNAc ligands presented
around the nanotube framework. Results also highlighted the high in vivo stability
of the synthetic radioemitter. Additional quantitative study to assess the organ
biodistribution and blood-clearance profile of the nanotube derivatives by direct
gamma counting reinforced the initial observations for a strong lung accumulation
and negligible blood content 3 minutes after administration (1% versus 27% for free
Na
125 I). The percentage of injected dose per gram tissue confirmed that more than
80% of
125 I persisted in the lung for 24 h only when inside SWNTs. In addition,
histological examination of different organs such as lung, liver, spleen, and kidneys
realized after administration of 28 further confirmed lung accumulation and
indicated no sign of necrosis or fibrosis. Finally, no cytotoxic response was obtained
from a human lung epithelial cell line (A549) following interaction with 28, even
with prolonged exposition times and concentrations up to 125 μg/mL, as determined
by in vitro cytotoxicity assay (LDH). In summary, the specific tissue accumulation
in the lung, coupled to high in vivo stability, prevented the leakage of radionuclide to
high-affinity organs (thyroid and stomach) and excretion, and resulted in ultrasensitive non-invasive imaging devices able to deliver an unprecedented radiodose
density.
Those examples thus paved the way for the conceptualization of optimized multitask organ-specific therapeutics and diagnostics constructed using CNT nanocapsules
surrounded by the multivalent presentation of relevant glycoconjugates.
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
313
The surface of these filled SWNTs was then covalently modified with bi-antennary
D-N-acetylglucosamine (GlcNAc) dendron to further improve the water dispersibility
and the biocompatibility of the nanosystems, and to provide the ability to target lung
tissues. For this, mild azomethine ylid 1,3-dipolar cycloaddition (Prato reaction) [67]
allowed the attachment of PEGylated glycoconjugate appendages together with the
2,3,5-triiodophenyl motif used as tagging agent, with the preservation of the tubular
structure and the closed ends of the filled SWNTs. Considering the fact that iodine
radioemitters used for treatment of thyroid cancer are still considered to be among the
most effective for systemic radiotherapy, the potential of the resulting functionalized
125
I-nanocapsule 28 to act as defined containers capable of localizing radionuclides
was investigated (Fig. 8a). Intravenous administration of 28, in the tail vein
of BALB/c mice was tracked in vivo using single-photon emission computed
tomography (SPECT). Results suggested strong differences in tissue and organ
biodistribution of the filled and glycosylated 28 compared to non-encapsulated
Na
125
I. Particularly, nanoencapsulation of
125
I prevented leakage of the radionuclide
to organs such as the thyroid and the stomach, known to have innate affinity for iodide,
and also avoided urinary or biliary excretion of the iodide, even after 7 days (Fig. 8b, c).
In fact, when 28 was administrated, the tissue distribution profile indicated
predominantly specific lung accumulation and persistent retention of the construct,
while no signals were detected in the thyroid, stomach, or bladder at t ¼ 0 or after
4 h, 24 h, or 7 days. This specificity was rationalized by the authors to be attributed to
the presence of lung-localized proteins able to bind the GlcNAc ligands presented
around the nanotube framework. Results also highlighted the high in vivo stability
of the synthetic radioemitter. Additional quantitative study to assess the organ
biodistribution and blood-clearance profile of the nanotube derivatives by direct
gamma counting reinforced the initial observations for a strong lung accumulation
and negligible blood content 3 minutes after administration (1% versus 27% for free
Na
125 I). The percentage of injected dose per gram tissue confirmed that more than
80% of
125 I persisted in the lung for 24 h only when inside SWNTs. In addition,
histological examination of different organs such as lung, liver, spleen, and kidneys
realized after administration of 28 further confirmed lung accumulation and
indicated no sign of necrosis or fibrosis. Finally, no cytotoxic response was obtained
from a human lung epithelial cell line (A549) following interaction with 28, even
with prolonged exposition times and concentrations up to 125 μg/mL, as determined
by in vitro cytotoxicity assay (LDH). In summary, the specific tissue accumulation
in the lung, coupled to high in vivo stability, prevented the leakage of radionuclide to
high-affinity organs (thyroid and stomach) and excretion, and resulted in ultrasensitive non-invasive imaging devices able to deliver an unprecedented radiodose
density.
Those examples thus paved the way for the conceptualization of optimized multitask organ-specific therapeutics and diagnostics constructed using CNT nanocapsules
surrounded by the multivalent presentation of relevant glycoconjugates.
Applications of Glyconanoparticles as “Sweet” Glycobiological. . .
313