CHAPTER I INTRODUCTION A.

Background

We know there is such a nanomaterial in the field of chemistry, and carbon nanotubes is one of nanomaterial which basically has a particular function. This is accompanied by the development of technology that is continuous. The unification of two things can create an application of carbon nanotubes that can provide benefits for humans. Because there are many deaths due to cancer, scientist has conducted research in the field of nanotechnology for cancer treatment. It involves the efforts of biologist and chemist researches, oncologist, immunologist, electronic and mechanical engineers. Even the last few years, the intellectual and monetery investments, from the scientific and economic communities of the greater nations in this field, reflect a great expectation toward the potential application of nanotechnology for a drastic reduction of cancer related deaths and for the development of personalized therapies. Because of these things, interesting for us to discuss the application of CNTs for cancer diagnosis and therapy in this paper, and certainly should be discussed first what it is CNTs and how the molecular structure of CNTs. B. Purpose Making of this paper is intended to assist understanding of our group about the application of CNTs in cancer diagnosis and therapy. The objective of the paper are: To find out what it is CNTs and how the molecular structure of CNTs, to know about the application of CNTs in cancer diagnosis and therapy that includes the workings of CNTs to do therapy and detect cancer. C. Hypothesis The size of CNTs are very small, it can penetrate tumors with a high-level specificity. CNTs can also delivering by some molecules to enter the cancer cells. Because of the characteristic of CNTs is interfering RNA, CNTs would activate the telomerase to reverse the coupled transcriptase to SWNTs and then detect tumors. It is certainly can treated cancer. Because of this reason, the application of CNTs-based offer the opportunity to introduce promising novel approaches to cancer treatment. D. General Description Carbon nanotubes are made of concentric walls in hexagonal pattern that measuring less than a few nanometers in diameter. Because of their small size, CNTs can penetrate tumors with a high-level specificity. By delivering genes, proteins or drugs directly to the cells, CNTs
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might allow to quickly detect and treat cancer at the early stage. The high symmetry structures of nanotubes are generally divided in three types, there are armchair, zigzag and chiral. CNTs could be functionalized by adsorbing near-infrared (NIR) light at wavelengths that are optically transparent to native tissue or by absorbing different molecules antibodies or antigens so that they may specifically target tumor cells. It can induce local heating of SWNTs in vitro to the cancer cell. Application of CNTs could allow simultaneously detection, imaging, and therapy of cancer. Additionally a variety of preclinical cancer models are available, suitable also for toxicity, biodistribution, biocompatibility studies.

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CHAPTER II BODY A. Definition of carbon Nanotubes Carbon nanotubes are made of one or several concentric walls in which carbon atoms are arranged in hexagonal pattern, measuring several tens of microns in length and less than a few nanometers in diameter. B. Moleculars Structures of Nanotubes The high symmetry structures of nanotubes are generally divided in three types, there are armchair, zigzag and chiral. These labels come from the distribution of the bonds along the perimeter of the nanotube describing zigzag or an armchair. The chiral family presents forms of lower symmetries with hexagons arranged helically along the axis of the tube. C. Application of Carbon Nanotubes in Cancer Diagnosis and Therapy The potential of cancer nanotechnology is in the ability to engineer vehicles with unique therapeutic properties that, because of their small size, can penetrate tumors with a high-level specificity. By delivering genes, proteins or drugs directly to the cells, CNTs might allow to quickly detect and treat cancer at the early stage. Thus, CNTs could be applied to tools for biosensing, imaguing and delivery, capable of selectively target the tumor and simultaneously be therapeutic. These rapidly emerging tools have brought fundamental advantages for cancer detection and treatment applications. For example, CNT-based sensor elements for selective multiplexed could sense cancer markers without the need of proble labelling. Futhermore, as already mentioned above, besides heterogenous functionalization, CNTs could provide localized delivery of therapeutic agents. CNTs absorb near-infrared (NIR) light at wavelengths that are optically transparent to native tissue. Irradiation with 880nm laser pulses can induce local heating of SWNTs in vitro; this effect can induce the releasing of the therapeutic molecules without harming cells or CNTs, and when internalized within a cancer cell, with sufficient heating can kill the cell. CNTs could be also functionalized by adsorbing different molecules, antibodies or antigens so that they may specifically target tumor cells. Kam et al, used folic acid (FA) and fluorescent tag conjugated SWNTs, to target tumoral cells highly expressing FA receptors cells in vitro, demonstrating that, SWNTs can be selectively internalized into cancer cells with specific tumor markers. SWNTs were actively internalized and then identified through the Fitc-tag by confocal microscopy analysis. In addition, NIR in vitro radiation of nanotubes, could selectively activate cell death without harming normal cells. Zhang Z. et al. Demonstrated that CNTs carrying interfering RNA (siRNA) can rapidly enter tumor cells, to exert the RNA interference on target gene expression. They used siRNA
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that specifically targeted murine telomerase to reverse coupled transcriptase to SWNTs by the functional group CONH-(CH2)6-NH3. The activations of telomerase is critical for immortalization, and it is detected in numerous malignant tumors, but not in most of normal cells. Hence, inhibition of telomerase activity is a major goal in targeted cancer therapy. The delivery of telomerase siRNA via CNTs silenced the target gene at the mRNA and protein levels, but also inhibited the proliferation of cancer cells in vitro, and suppressed tumor growth in mouse models, upon intralesional injection. The use of CNTs as a vehicle for delivery of siRNA an cancer cells, presents great promises. Liu Z. et al. have recently described the in vivo distribution of radio-labelled SWNTs in mice by positron emission tomography (PET). The unique one-dimensional shape and flexible structure of SWNTs enables a polyvalence effect and enchances tumor binding affinity. Efficient targeting of integrin positive tumour in mice was achieved with SWNTs coated with polyethyleneglycol (PEG) chains, linked to an arginine-glycine-aspartic acid (RGD) peptide. They did not observe toxicity or negative health effects. However, SWNTs functionalized with PEG showed elevated stability in vivo, and moreover, relatively slow excretion and high accumulation in the liver of SWNTs was observed. Other authors evaluated the biodistribution of antibody-functionalized radiolabeled CNTs, develoved as a platform, with attached antibody, metalion chelate, and fluorescent chromophoremoieties, to respectively effect specific targeting, to carry and deliver a d report location. Although the constructs demonstrated to perform their function in targeting cancerous cells, its not certain if the accumulation in liver and kidney can be acceptable for Moreover, the covalent attachment of antibody molecules to the CNTs dramatically altered the kidney biodistribution and pharmacokinetics. Supplementary investigation, to predict modifications that could affect the pharmacokinetic profile and to understand the reasons for accumulation and clearence of CNTs in normal tissue, are crucial for further development. Discovery in CNTs applications is in progress, with important implications for the management of cancer patients in the near future. The development of integrated platforms could allow simultaneously detection, imaging and therapy of cancer. Utilizing a tumor-py, agents can be achieved an the site of action with minimal systemic exposure, reducing toxicity and increasing its availability. Application of cancer diagnosis and therapy in nanoscale component or devices, offer the opportunity to introduce promising novel approaches to cancer treatment, delivering multiple drugs in a timed manner and at different locations in the body. The plurality of functions potentially performed by the CNTs perfectly fits with the complex strategy required for cancer diagnosis and treatment. Moreover the cost benefit in
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term of toxicity is more favourable because of the severity of the disease, and the length of treatment should be necessarily short. Additionally a variety of preclinical cancer models are available, suitable also for toxicity, biodistribution, biocompatibility studies. Taken together, these considerations make cancer management the most likely field of application for CNTs technology in the near future.

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CHAPTER III CONCLUSION Carbon nanotubes are made of one or several concentric walls in which carbon atoms are arranged in hexagonal pattern, measuring several tens of microns in length and less than a few nanometers in diameter.The high symmetry structures of nanotubes are generally divided in three types : armchair, zigzag and chiral. Technology of CNTs , can penetrate tumors or cancer with a high-level specificity and CNTs might allow to quickly detect and treat cancer at the early stage.

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References

Habenicht, Kilina. 2009. Excitonic and Vibrational Dynamics in Nanotechnology. Pan Stanford Publishing : Singapore.

Hai-Chen Wu, et. al. 2010. Chemeistry of carbon nanotubes in biomedical application. Royal Society of Chemistry. http://pubs.rsc.org/en/content/articlelanding/2010/jm/b911099m. Accessed on December 24th. Rakov, EG 2001. The chemistry and application of carbon nanotubes. Russian Academy of Sciences
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http://www.physicsAccessed on

online.ru/PaperLogos/7326/files/Full_text_English_version.pdf. December 24 .

Silvana, Fiorito. 2008. Carbon Nanotubes Angels or Demons. Pan Stanford Publishing : Singapore

Urquhart, James. 2010. No nanotubes fertility risk. Royal Society of Chemistry. http://www.rsc.org/chemistryworld/News/2010/August/08081002.asp. December 24th. Accesed on

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Appendices
Questions 1. 2. 3. What are the advantages of carbon nanotubes application in cancer diagnosis and therapy? Is there relation between CNTs with technology? If the answer yes,please mention it! Is there any inhibitor to manipulate CNTs so that can be applied in various applications of CNTs? Answers 1. The advantages of CNTs application in cancer diagnosis and therapy are we just require a low cost to detect and treat the cancer. Besides it, cancer treatment that we do, does not require a long time. 2. The answer is yes, there is relation between CNTs with technologyCarbon nanotube are the desirable materials in nanotechnologies. Several aspects of SWCNTs account for their

promise in a number of technological applications : a decolized mobile fi- electron system, extraordinary mechanical, electronic and optical properties, and the ability to tune this properties by specifying the tube geomethry. 3. Yes, there are inhibitors in manipulating CNTs. Inhibitors are a few characteristic of CNTs. They are: 2) very low solubility of CNTs in organic solvents and water; 3) inert properties of pristine CNTs many chemical reaction under conditions. Pictures and the explanations

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Picture 5

Picture 6

Explanation of Picture 5
Selective targeting and killing of cancer cells, (a) Chemical structure of PL-PEG-FA and PLPEC-FITC synthesized by conjugating PL-PEG-NH2 with FA or FITC, for solubilizing individual SWNTs. (b) (Upper) Schematic of selective internalization of PL-PEC-FA-SWNTs into folate-overexpressing (FR+) cells via receptor binding and then NIR 808-nm laser radiation. (Lower) Image showing death of FR+ cells with rounded cell morphology after the laser radiation (808-nm at 1.4 W_cm2 (or 2 min). (Inset) Higher magnification image shows details of the killed cells, (c).(Upper) Schematic of no internalization of PL-PEC-FA-SWNTs into normal cells without available FRs. (Lower) Image showing normal cells with no internalized SWNTs are unharmed by the same laser radiation condition as in (b). (Inset) Higher magnification image shows a live normal cell in stretched shape, (d) Confocal image of FR+ cells after incubation in a solution of SWNTs with two cargoes (PL-PEC-FA and PLPEC-FITC). The strong green FITC fluorescence inside cells confirms the SWNT uptake with FA and FITC cargoes, (e) There is little green fluorescence inside cells, confirming little uptake of SWNTs with FA and FITC cargoes in normal cells

Explanation of Picture 6
Injection of hTERTsiRNA: SWNT + complexes suppresses HeLa xenograft growth. A to C, specific gene silencing induced by hTERTsiRNA: SWNT+ complexes in human HeLa cells. The level ol hTERT transcripts (A), hTERT protein (B), and telomerase activity (C) was assayed in untreated control HeLa cells (lane 1) and after treatment of HeLa for 24 hours with 2 nmol/L of mTERTsiRNA alone (lane 2), mock siRNA:SWNTs-l- (lane 3), and hTERTsiRNA: SWNTs-l (lane 4). D and E, in vitro suppression ol humanH- HeLa cell proliferation and induction of senescence by hTERTsiRNA: SWNT+ complexes; untreated control HeLa cells (left) and after treatment of HeLa for eight days with 2 nmol/L of mTERTsiRNA alone, mock siRNA: SWNTs+, and hTERTsiRNA: SWNTs + (middle right and right). E, the number of blue-stained cells was counted in at least 10 fields at x400 magnification and expressed as a percentage of total cell number. F to H, injection of hTERTsiRNA: SWNTs+ retarded HeLa tumor growth. HeLa cells (2 x 10" per mouse) were injected s.c into right leg of nude mouse (five mice per group). After one week, when diameter of tumors was f2.5 mm, hTERTsiRNA: SWNTs or siRNA alone or mock siRNA: SWNT+ complexes were injected into the tumor at multiple points (f 00 AL of 10 nmol/L siRNA per mouse). F, one representative of per group of control animals (left), hTERTsiRNA alone (middle left), mock siRNA: SWNT + (middle right), and hTERTsiRNA: SWNTs (right). C, columns, mean tumor size; bars, SE. H, columns, mean tumor weight Page 9 of 9 Carbon Nanotubes