Nanotechnology tackles tumours

Single-walled carbon nanotubes can now effectively target tumours in mice, which suggests that nanotubes could form the basis of a safe drug-delivery system for cancer therapy.

In addition to their well known electronic, optical and mechanical properties, carbon nanotubes could also have applications in drug delivery and other areas of medicine. A drug-delivery system is generally designed to improve the distribution and performance of drug molecules. Carbon nanotubes have already been used to deliver drugs, peptides, nucleic acids and other loads in a variety of cell culture systems1,2. The load can be carried either inside or outside the nanotube, and carefully chosen molecules attached to the outside ensure that it is delivered to a specific target. Moreover, carbon nanotubes absorb radiation efficiently in the near infrared region, so the local heating that occurs when they are irradiated with a laser can be used to selectively destroy cancerous cells3.

To date, however, there have been no studies on the use of carbon nanotubes to deliver drugs in live animals. On page 20 of this issue, Hongjie Dai, Xiaoyuan Chen and colleagues4 at Stanford University report that single-walled carbon nanotubes wrapped in polyethylene glycol (PEG) polymer and labelled with specific bioactive peptides can efficiently reach tumour tissues in mice with no apparent toxicity or negative health effects. This work sheds new light on the use of carbon nanotubes as a drug carrier and its distribution in an animal system.

For safe biomedical applications of carbon nanotubes in the human body, including drug delivery, we need to learn about their biodistribution and pharmacokinetics (that is, how the drug and its carrier are distributed, absorbed, metabolised and eliminated in the body). At present very little is known; so far only two papers have reported results on the biodistribution of carbon nanotubes in mice5,6.

Dai, Chen and colleagues quantitatively measured the distribution in mice of nanotube–PEG with and without the peptide. In both cases, the complexes circulated in the blood for a long time and accumulated in the liver and spleen, contrary to a previous report where nanotubes were excreted quickly and there was no uptake in the liver and spleen6. Additionally, nanotube–PEG complexes bearing peptides accumulated efficiently in the tumour.

The use of carbon nanotubes in drug delivery has been hindered because nanotubes are not soluble in the physiological environment. To solve this problem, hydrophilic groups can be covalently bonded to the nanotube surface, but this can adversely affect many of the properties that make SWNTs attractive for applications7. The Stanford team therefore non-covalently bound PEG around the SWNT to make it soluble. On the PEG, they then linked a radionuclide 64Cu for tracing purposes and the bioactive peptide RGD (arginine–glycine–aspartate sequence) that targets tumour receptors in the mice8 (Fig. 1a). This complex was surprisingly stable in vivo with little detachment of the radionuclide, and it retained the useful intrinsic optical properties of the SWNTs that allow the accurate study of these nanotubes as drug delivery systems.

Figure 1: Targeting tumours with single-walled carbon nanotubes (SWNTs).

a, A carbon nanotube wrapped with polyethylene glycol (PEG): some of the PEG contain the radioactive isotope 64Cu (blue dots) for tracing, whereas others contain the bioactive peptide RGD (red triangles) that targets the tumour. b, SWNTs were injected into the tail of a mouse that had a tumour (green) implanted in its front foot. The RGD peptide targets and binds to the receptors (purple Ys) in the tumour. For clarity, different parts are drawn at arbitrary scales.

The 64Cu emits two types of radioactive radiation: γ-rays, which can be used for radiotracing, and positrons (β+) for positron emission tomography (PET) imaging. The peptide, meanwhile, adheres to newly formed tumour microvessels or the cell membrane of tumours and impairs cancer growth.

A common criterion for evaluating the potential of an anticancer drug is the specific uptake by tumours expressed as the T/N ratio, where T is tumour uptake of a drug and N is the uptake of neighbouring healthy tissues. A T/N ratio of 4–5 or more means the anticancer drug candidate deserves further study for its therapeutic potential. Dai and co-workers report a satisfactorily high T/N ratio of over 15 for the nanotube–PEG–peptide system and show that uptake levels as monitored with PET images were very consistent with those measured by 64Cu radioactivity distribution. This high tumour accumulation was due to the long blood circulation, good targeting, and multiple binding of tumour receptors by the dense number of peptides along the nanotube.

This work shows that carbon nanotubes attached with a tumour-targeting peptide can indeed function as an anticancer drug-delivery vehicle with no apparent health complications in the mice. As a good number of peptides are known to be useful for cancer therapy9, Dai and colleagues have opened up a new field in non-covalently modifying carbon nanotubes with different types of bioactive peptides for a variety of potentially safe in vivo biomedical applications.

The fact that the biodistribution data as measured by radioactivity and PET images were consistent with one another proves that the experimental results are very reliable. Furthermore, Dai and colleagues were able to use Raman spectroscopy to directly detect nanotubes in a homogenous suspension solution of mouse tissue because the non-covalently modified SWNTs retained their optical properties. Concurrently measuring the therapeutic application and biodistribution of these nanotube complexes presents a convincing case for the efficacy of this system. This is true from both an application and safety standpoint because we are now sure the biodistribution data correlates with the therapeutic strategy.

Even though Dai and colleagues have achieved a notable breakthrough, there are factors that still need to be explored before nanotubes can be used for drug delivery. First, learning to effectively load the drug onto the nanotubes may lower the required drug dosage. Second, reliably targeting and triggering drug release at the therapeutic site is desired for a therapy with least side effects. Third, and also of great importance, is the long-term fate of these nanotube systems in the body. Although there is still a long way to go, this work by the Stanford group brings us one step closer to understanding the current state of SWNTs in the biomedical arena.


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Liu, Y., Wang, H. Nanotechnology tackles tumours. Nature Nanotech 2, 20–21 (2007).

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