CNTs are safe

The disease potentials of CNTs were examined to check for similar affect by asbestos – in Scotish university they “injected” short and long nanotubes into body of mice, and found that short ones show no effect but longer ones caused inflation. For human beings the concern is confined to laboratory atmosphere!

An ongoing work for designing synthetic materials that can enter into membrane cells and other materials can be attached to them for direct delivery such as drugs - MIT researchers managed to create a shell around gold nanoparticles and sending them into the cells with no damage – they pointed to unknown process here which probably is about the similar chemistry that enables them to enter into cell membranes without any interruption to cells! The structural composition of functionalized group is impor-tant in terms of penetration into cells.

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Kam et al have shown that folic acid can be adsorbed onto the carbon nanotubes to allow specific binding to cancer cells that overexpress folate receptors and subsequent receptor-mediated endocytosis. Tumor cells that had internalized the folic acid–bound carbon nanotubes were selectively destroyed upon irradiation with NIR, whereas receptor-free normal cells that had not internalized these carbon nanotubes were not harmed by NIR irradiation.

I see notes on a novel property of SWNTs - heat release in a radiofrequency (RF) field – which is to be used to produce thermal cytotoxicity in malignant cells. Direct injection of SWNTs into tumours followed by immediate RF field treatment was shown to be effective in experiment on rabbits. (4)

Doping SWCNT by PTX, a widely used cancer chemotherapy obtained a water soluble SWNT-PTX which was far more efficient in suppressing tumour growth than clinical Taxol because of 10 times more uptake through enhanced permeability and retention. (3)

Also activation of chemical properties of CNTs exterior binding of anti-cancer molecules was examined to target cancer cells and for versatile drug delivery. CNTs, with recognizable epitopes - that is for identification by the immune system - have resulted in engulfing of f-CNTs by cancerous cells only (1). While encapsulation of doxorubicin in CNTs increased its accumulation and penetration in tumours in terms of both the percentage of cells that were reached by the drug and the intracellular levels that were attained. (2)

SWNTs were reported to have the high ability to promote electron-transfer reactions in electrochemical measurements (Wang 2004). They have the ability to change electron transfer reactions when used as an electrode modifying material. This modified electrode showed a dramatic improvement in respect of the electrochemical oxidation of dopamine, epinephrine, ascorbic acid and norepinephrine. (5)

SWNTs behave as a well-defined metallic, semiconducting, or semi-metallic structure, depending on chirality and diameter. They can then be used as cancer biomarkers. (4) The chirality of SWNTs determines their conductivity, allowing for their potential development into a wide variety of SWNT-based electronic switching devices.
An application to make carbon nanotubes respond to magnetic forces was studied by growing them by plasma-enhanced chemical vapour deposition (PECVD) with ferromagnetic catalyst nickel particles enclosed in their tips to transport molecules into cancer cells. (6) The filling of CNTs with magnetic materials offers the potential for hyperthermia applications. while the insertion of NMR active substances allows the usage as markers and sensors.



(1) http://www.nature.com/nrd/journal/v4/n2/abs/nrd1632.html

(2) Carbon nanotubes as functional excipients for nanomedicines: I. pharmaceutical properties, ScienceDirect, 2008
(3) Zhuang L, Drug Delivery with Carbon Nanotubes for In vivo Cancer Treatment, Cancer Research J, 2008
(4) Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field, wiley, 2007 http://www3.interscience.wiley.com/journal/116834125/abstract
(5) Compton, Abrasive immobilization of carbon nanotubes on a basal plane pyrolytic graphite electrode: application to the detection of Epinephrine, Oxford Univ, 2004
(6) Yang D et al, Magnetic lymphatic targeting drug delivery system using carbon nanotubes . Medical Hypotheses , Volume 70 , Issue 4 , Pages 765 - 767
(7)

The long-term accumulation and toxicity of intravenously injected SWCNTs in the main organs (such as liver, lung and spleen) in mice were carefully studied. Although SWCNTs stayed in mice over 3 months, they showed low toxicity to mice. Previous studies have reported the cytotoxicity, pulmonary and skin toxicity of SWCNTs (Smart et al., 2006). Pristine SWCNTs have been proven to be cytotoxic, inducing the cell viability loss (Jia et al., 2005), oxidative damage (Pulskamp et al., 2007), inflammation (Brown et al., 2007) and apoptosis (Cui et al., 2005). The cytotoxicity depends on the aggregation degree and pretreatment of SWCNTs samples (Wick et al., 2007). It is also suggested that the cytotoxicity of pristine SWCNTs could be reduced via chemical functionalization (Sayes et al., 2006). In the pulmonary and skin toxicity studies, pristine SWCNTs also show considerable toxicity, including animal death, inflammation and other clinical signals (Smart et al., 2006). Only a very recent pilot study shows polyethylene glycol (PEG) modified SWCNTs are non-toxic after intravenous (i.v.) injection by using very limited animals (Schipper et al., 2008). The decreasing glutathione (GSH) level and increasing malondialdehyde (MDA) level suggest that the toxicity of SWCNTs might be due to the oxidative stress.


Drug Delivery Trends in Clinical Trials and Translational Medicine, 2008, A webbased clinical trial registry at www.clinicaltrials.gov was created for locating data from federally and privately supported clinical trials.

Not only dose matters but the rate and amount of uptake proved to be of concern both in terms of toxicity and treatment functions! One cancer study found that although dendrimer showed less effectiveness in an equivalent dose and same time span compared to doxorubicin, but when examined on tumour cells it performed far better – and the cause was found to be slower uptake by the tumour cells! Dose-management is crucial in all aspects of assessment of toxicity as was highlighted in Charged Particle Theory in their capacity to treat cancer tumours that was presented by Prof Ken Peach who is directing well funded projects in cancer therapy with Protons, and is based on distortion of healthy tissues in other radiation therapy!

Thus, nanotube drug delivery is promising for high treatment efficacy and minimum side effects for future cancer therapy with low drug doses. [Cancer Res 2008;68(16):6652–60]

Single-Dose Drug-Loaded Dendrimer Cures Mice of Colon Cancer, NCI Alliance for Nanotechnology in Cancer, National Cancer Institute, 2006
http://nano.cancer.gove

Lee CC, A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. http://www.ncbi.nlm.nih.gov/pubmed/17075050?dopt=AbstractPlus

Liu Z et al, Stanford Univ., Drug Delivery with Carbon Nanotubes for In vivo Cancer Treatment, American Ass. For Cancer Research 68, Aug 2008
http://cancerres.aacrjournals.org/cgi/content/abstract/68/16/6652