Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging

Abstract

Functionalization of nanomaterials for precise biomedical function is an emerging trend in nanotechnology. Carbon nanotubes are attractive as multifunctional carrier systems because payload can be encapsulated in internal space whilst outer surfaces can be chemically modified. Yet, despite potential as drug delivery systems and radiotracers, such filled-and-functionalized carbon nanotubes have not been previously investigated in vivo. Here we report covalent functionalization of radionuclide-filled single-walled carbon nanotubes and their use as radioprobes. Metal halides, including Na(125)I, were sealed inside single-walled carbon nanotubes to create high-density radioemitting crystals and then surfaces of these filled-sealed nanotubes were covalently modified with biantennary carbohydrates, improving dispersibility and biocompatibility. Intravenous administration of Na(125)I-filled glyco-single-walled carbon nanotubes in mice was tracked in vivo using single-photon emission computed tomography. Specific tissue accumulation (here lung) coupled with high in vivo stability prevented leakage of radionuclide to high-affinity organs (thyroid/stomach) or excretion, and resulted in ultrasensitive imaging and delivery of unprecedented radiodose density. Nanoencapsulation of iodide within single-walled carbon nanotubes enabled its biodistribution to be completely redirected from tissue with innate affinity (thyroid) to lung. Surface functionalization of (125)I-filled single-walled carbon nanotubes offers versatility towards modulation of biodistribution of these radioemitting crystals in a manner determined by the capsule that delivers them. We envisage that organ-specific therapeutics and diagnostics can be developed on the basis of the nanocapsule model described here.

Modulation of Carbon Nanotubes' Perturbation to the Metabolic Activity of CYP3A4 in the Liver

“…[ 38 ] Previous studies have also shown that well-dispersed CNTs are excreted via a biliary pathway after hepatocyte uptake. [ 39,40 ] Hepatocytes in the liver can clear foreign particles via an endocytosis mechanism. [ 41,42 ] Our TEM ,C)).…”

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…The covalent functionalization of the radionuclidefilled SWNTs were used as radio probes [210] . The intravenous (IV) administration of these 125 I-loaded SWNTs was tracked in vivo using SPECT.…”

Medical imaging in personalised medicine: a white paper of the research committee of the European Society of Radiology (ESR)

“…A major advantage of nanoparticles for theranostics would be the high payload of both therapeutic agent and imaging probe that can be delivered to the target tissue. Specific examples of theranostic agents currently under investigation include liposomal vesicle formulations containing cytostatic drugs and MR contrast agents [28,29], carbon nanotubes as multifunctional carriers for radioisotopes for treatment and imaging [30], and dendriworms for efficient delivery of siRNA (small interfering RNA) visualised by optical imaging or MRI [31]. An additional new approach in theranostic strategies is 'cellular theranostics'.…”