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Posted: Aug 02, 2012

Nanoparticle-corked carbon nanotubes as drug delivery vehicles

(Nanowerk Spotlight) Nitrogen-doped carbon nanotubes (CNTs) have been extensively investigated for fuel cell applications due to their excellent electrocatalytic properties (see for instance our previous Nanowerk Spotlight: "Nitrogen-doped carbon nanotube catalyst systems for low-cost fuel cells"). However, their biomedical applications were comparatively less investigated despite reports of their better biocompatibility.
When considering carbon nanotubes for drug delivery applications, it is desirable to develop strategies that allow utilize their hollow inner cavities for maximum loading capacity. Small size and facile surface modification are also preferable with regard to their biomedical compatibility.
Nitrogen-doped CNTs have been already previously demonstrated to have better biocompatibility and mitigated cytotoxicity as compared to traditional undoped pristine CNTs (see our Nanowerk Spotlight: "A first report on the biocompatibility of nitrogen-doped carbon nanotubes").
Taking advantage of this, Alexander Star, an associate professor in the Department of Chemistry at the University of Pittsburgh, and his team used nitrogen doping of CNTs which resulted in formation of cup-shaped compartments in CNTs uniquely suitable for encapsulation. The resulting nitrogen-doped carbon nanotube cups (NCNCs or nanocups) – a new cup-shaped carbon nanomaterial with diverse reactivity – can be corked by gold nanoparticles to form enclosed nanocapsules. The nanocups were obtained from fibrous nitrogen-doped CNTs by ultrasonication.
"With their cup shapes, controlled sizes, and versatile chemical properties, the nanocups can serve as ideal drug delivery vehicles with multifunctionality for targeted drug delivery and better biocompatibility," Star tells Nanowerk.
The team reported their work in the July 13, 2012 online edition of ACS Nano ("Corking Carbon Nanotube Cups with Gold Nanoparticles").
Lund
Upper panel: Schematic illustration showing the process of obtaining individual carbon nanocups from as-synthesized fibrous nitrogen-doped CNTs by ultrasonication and the subsequent "corking" of the nanocups with gold nanoparticles (GNPs). Lower panels: corresponding transmission electron microscopy (TEM) images of as-synthesized nitrogen-doped CNTs (left), separated individual nanocups (middle) and nanocups corked with GNPs (right).(Reprinted with permission from American Chemical Society)
This work was motivated by the unique morphology of nitrogen-doped CNTs. "Due to the nitrogen-doping, the tubular structures of CNTs are changed to compartmented structures resembling many individual nanocups stacked up," explains Star. "These hollow nanocups, possessing nitrogen functionalities, can serve as potential nano-containers if successfully isolated out. Using high-resolution transmission electron microscopy (TEM) analysis, we found that the adjacent nanocups have no covalent interaction with each other but merely physically stacked, which allowed the mechanical separation of the nanocups by ultrasonication ('shaking')."
To be utilized, the stacked cup-shaped nitrogen-doped CNTs need to be separated in order to obtain individual nanocups. Previous attempts of nanocup separation by Star's team involved grinding with a mortar and pestle but resulted only in a limited yield ("Synthesis, Characterization, and Manipulation of Nitrogen-Doped Carbon Nanotube Cups"). In this new work, the researchers used high-intensity ultrasonication, which resulted in a much higher yield.
"By adopting the quantitative Kaiser test, we for the first time determined and quantified the amine groups as the major functionalities on the separated nanocups, and we subsequently explored the reactivity and distribution of the amine groups by functionalization with gold nanoparticles and found that the amine groups were preferentially located at the open rims of the nanocups," says Pitt graduate chemistry student Yong Zhao who was the paper's lead author. "Taking advantage of this fact, we managed to effectively cork the nanocups by gold nanoparticles with commensurate sizes to create a new type of cup-shaped nanocontainers with corked opening."
The potential application of this work is to use the nanocups as nanoscale containers, especially as drug delivery vehicles. Star points out that the gold nanoparticle corked nanocups have all the desired properties for biomedical applications, including their hollow, self-confined cup structures, diverse reactivity, and biocompatibility. To make an effective drug delivery vehicle, the surface of nanocups can be functionalized with different moieties such as bio-recognition groups or fluorescent labels. The gold nanoparticle corks can be designed to be open under certain stimuli, to achieve a controlled release of drugs.
There still are some issues the team has to overcome. Although they managed to obtain the individual nanocups at a higher yield compared to previous attempts, incompletely separated nanocups still frequently exist. They appeared as short stacks of cups of several units. Star says that size-exclusion separation, such as nanopore-sized filtration, can further increase the concentration of the individual nanocups.
Another problem is that it is hard to cork every separated nanocups with gold nanoparticles due to the scarcity of intrinsic amine groups and the heterogeneous morphology of nanocups. Although gold nanoparticles have a preferential interaction with the opening of the nanocups, the best percentage of corked nanocups was about 23%. Star's team is currently working on improving efficiency of their method.
Going forward, the scientists are planning to functionalize the corked nanocups with diverse functional groups for in vivo experiments, for example, fluorescent groups that allow the imaging of the nanocups in the tissue.
"In addition, we are investigating the biodegradation behavior of the nanocups using peroxidase enzymes which, as we reported previously (see our previous Nanowerk Spotlight: "Biodegradation of carbon nanotubes could mitigate potential toxic effects"), can enzymatically degrade both single-walled and multiwalled carbon nanotubes," says Star. "The challenges facing future research in this area lie in the design of specific cell-targeting and controlled release of drugs in the target cells."
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