Elsevier

Inorganica Chimica Acta

Volume 495, 1 September 2019, 118933
Inorganica Chimica Acta

Research paper
In vivo behaviour of glyco-NaI@SWCNT ‘nanobottles’

https://doi.org/10.1016/j.ica.2019.05.032Get rights and content

Highlights

  • Roles played by glycans on carbon nanotubes in controlling accumulation were tested.

  • Nanotubes carrying ‘cold’ or ‘hot’ salt cargoes decorated with glycans.

  • Altered glycans and administration suggests distribution is primarily physiological.

  • Primary role of glycan appears to be in aiding the dispersibility of the CNTs.

Abstract

Carbon nanotubes are appealing imaging and therapeutic systems. Their structure allows not only a useful display of molecules on their outer surface but at the same time the protection of encapsulated cargoes. Despite the interest they have provoked in the scientific community, their applications have not yet been fully realised due to the limited knowledge we possess concerning their physiological behaviour. Previously, we have shown that the encapsulation of radionuclide in the inner space of glycan-functionalized single-walled carbon nanotubes (glyco-X@SWCNT) redirected in vivo distribution of radioactivity from the thyroid to the lungs. Here we test the roles played by such glycans attached to carbon nanotubes in controlling sites of accumulation using nanotubes carrying both ‘cold’ and ‘hot’ salt cargoes decorated with two different mammalian carbohydrates, N-acetyl-d-glucosamine (GlcNAc) or galactose (Gal)-capped disaccharide lactose (Gal–Glc). This distinct variation of the terminal glycan displayed between two types of glycan ligands with very different in vivo receptors, coupled with altered sites of administration, suggest that distribution in mammals is likely controlled by physiological mechanisms that may include accumulation in the first capillary bed they encounter and not by glycan-receptor interaction and that the primary role of glycan is in aiding the dispersibility of the CNTs.

Introduction

The inner cavities of carbon nanotubes (CNTs) can accommodate a wide range of guest species [1], [2], [3], [4]. Unprecedented structures and properties compared to those of the same material in the bulk can be observed when they are confined [5], [6], [7], [8], [9], [10], [11]. In the biomedical field, contrast agents and therapeutic compounds can be either attached to the external CNT walls or confined within the cavities of the CNTs [12], [13], [14], [15], [16], [17], [18]. The latter is attractive because CNTs can offer striking protection to chosen payloads, avoiding their interaction with the biological milieu [19].

Several strategies have been developed for the encapsulation of materials inside carbon nanotubes. Once filled, unless there is a strong interaction between the host nanotubes and the guest species, the ends of the CNTs need to be sealed/closed to allow selective purification from non-encapsulated materials left external to the CNT. Heating nanotubes together with inorganic salts at high temperatures allows capillary permeation of the melted salts inside the nanotubes with the spontaneous closure of the extremities during the cooling process [20], [21]. The salts remain stably confined in the form of ‘nanocrystals’ inside the nanotubes while leaving the outer surface essentially unaffected, and so ready to be modified by organic molecules.

As-produced, CNTs are insoluble in almost any aqueous solution and organic solvent, and have been suggested to be toxic to mammalian cells [22], thereby presenting perceived limitations to their biological applications [23], [24], [25], [26], [27]. Functionalization of CNT side-walls with biologically- and biotechnologically- relevant molecules (including polymers [28], peptides [29], [30], nucleic acids [31] and carbohydrates [32], [33]) allows the generation of potentially stable and biocompatible dispersions. For example, non-covalent binding of aromatic molecules by π–π stacking onto the surface of the nanotubes [34] or covalent modification of their polyarenic surface [35] allow loading of multiple molecules along the length of the nanotubes.

We have previously shown that encapsulation of radionuclide into the inner space of glycan-functionalized single-walled carbon nanotubes (glyco-X@SWCNT) may be achieved by molten filling and then covalent modification, allowing in vivo redirection of the distribution of the associated radioactivity from the thyroid to the lungs [33]. Here, we use steam-purified and shortened single-walled carbon nanotubes (SWCNTs) [36] filled with both ‘cold’ (NaI) and ‘hot’ (Na125I) cargoes and subsequent functionalization with different carbohydrates to explore the basis and role of glycan in this redistribution.

Section snippets

Purification of SWCNTs

Chemical vapour deposition (CVD) grown SWCNTs, were provided by Thomas Swan & Co. Ltd (Elicarb®). Steam purification was carried out in order to remove the amorphous carbon and graphitic shells formed during the synthesis [36]. Steam treatment was simultaneously employed to open the SWCNTs ends. For this purpose, 1 g of as-received SWCNTs were ground with agate mortar and pestle and then placed inside a tubular furnace. Steam was introduced by bubbling argon through hot water. The temperature

Preparation of ‘cold’ glyco-NaI@SWCNTs

To prepare the nanotubes for filling they were first treated with steam, followed by an HCl (aq) wash, in order to remove graphitic nanoparticles, amorphous carbon and metal catalysts that remain as impurities from their generation [36]. This method also results in simultaneous shortening of the nanotubes via a process believed to involve oxidation and decarboxylation of more reactive carbon sites present at their tips [36]. TEM images of both as-received and steam-purified SWCNTs are shown in

Conclusions

Functionalized and glycosylated nanotubes can act as ‘nanocapsules’ or ‘nanobottles’ to redirect the accumulation of inorganic radionuclide ‘cargo’ concealed in their inner void (here iodide) from a natural physiological target (here thyroid) [50] to alternative targets. At the functionalization loadings used here, different glycosylation patterns on these glyco-‘nanobottle’ constructs did not modulate in vivo distribution profiles. Instead, these appear to only aid dispersibility; these

Acknowledgements

This works was financially supported by EU FP7-ITN Marie-Curie Network programme RADDEL [grant number 290023] and the EU FP7-Integrated Infrastructure Initiative–I3 programme ESTEEM2 [grant number 312483]. We also acknowledge financial support from Spanish Ministry of Economy and Competitiveness through the “Severo Ochoa” Programme for Centres of Excellence in R&D [grant numbers SEV-2015-0496, ICMAB; SEV-2017-0706, ICN2]. The ICN2 is funded by the CERCA programme. We would like to thank Thomas

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