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World Review of Science, Technology and Sustainable Development, Vol. 4, Nos. 2/3, 2007

Nanotechnology in cancer prevention, detection and treatment: bright future lies ahead G. Ali Mansoori
Departments of Bio and Chemical Engineering, University of Illinois at Chicago, 218 SEO, 851 S, Morgan St. (M/C 063), Chicago, IL 60607-7052, USA E-mail: mansoori@uic.edu

Pirooz Mohazzabi*
Department of Physics, University of Wisconsin – Parkside, Kenosha, WI 53141, USA E-mail: pirooz.mohazzabi@uwp.edu *Corresponding author

Percival McCormack
Department of BioEngineering, University of Illinois at Chicago, 218 SEO, 851 S. Morgan St. (M/C 063), Chicago, IL 60607-7052, USA E-mail: pmccorm@uic.edu

Siavash Jabbari
Department of Radiation Oncology, University of California – San Francisco 1600 Divisadero Sreet, Suite H1031, San Francisco, CA 94143-1708, USA E-mail: siavashjabbari@gmail.com
Abstract: This paper is an overview of advances and prospects in applications of nanotechnology for cancer prevention, detection and treatment. We begin with a brief description of the underlying causes of cancer. Then we address preventive treatment, disease-time treatment, and diagnosis in the context of some of the most recent advances in nanotechnology. Nanoparticle science is also briefly addressed as the foundation upon which most nanotechnology cancer therapy is based. It is demonstrated how nanotechnology can help solve one of the most challenging and longstanding problems in medicine, which is how to eliminate cancer without harming normal body tissue.

Copyright © 2007 Inderscience Enterprises Ltd.

Nanotechnology in cancer prevention, detection and treatment
Keywords: cancer; diamondoid; folate receptor; hyperthermia method; nanoparticle; melanoma; nanocrystal; nanobiotechnology; nanotechnology; quantum dot. Reference to this paper should be made as follows: Ali Mansoori, G., Mohazzabi, P., McCormack, P. and Jabbari, S. (2007) ‘Nanotechnology in cancer prevention, detection and treatment: bright future lies ahead’, World Review of Science, Technology and Sustainable Development, Vol. 4, Nos. 2/3, pp.226–257. Biographical notes: G. Ali Mansoori is a Professor of Bio and Chemical Engineering. He received his undergraduate education at Tehran University, his graduate education at the Universities of Minnesota and Oklahoma, all in chemical engineering, and he was a postdoctoral fellow at Rice University. He has published extensively in the areas of nanotechnology, biotechnology, energy technology, thermodynamics and statistical mechanics. He is a Consultant and Lecturer to numerous bio, chemical, energy and health-related industries and research centres. For his research achievements he has received numerous recognitions including the UNESCO medal of fundamental science, Algorithm scientific international award and the Russian Academy of Natural Sciences Kapitsa gold medal. Pirooz Mohazzabi is a Professor of Physics at the University of Wisconsin-Parkside. He received his undergraduate degree in Chemistry from Tehran University in 1969, his MSc and PhD Degrees in Materials Science and Engineering from the University of California, Berkeley in 1972 and 1975, respectively. He has over 30 years of research and teaching experience in physics, materials science and chemistry. He has published extensively in the areas of condensed matter physics, materials science, thermodynamics and statistical mechanics, nanotechnology, applied mathematics, classical and quantum mechanics, as well as pedagogical aspects of physics. Percival McCormack is an Adjunct Professor of Bioengineering, Biophysics and Physiology. He has BA (Physics and Mathematics), MSc (Computer Science), PhD (Nuclear Physics), ScD (published work) and MD (medicine) all from Trinity College, Dublin. He received many fellowships and honours including senior medical research fellow (National Cancer Institute), fellow (Institute of Physics, London), fellow (Royal Society of Medicine, London), Navy Commendation Medal and German Navy Cross of Honour. He held many positions including Professor of Engineering Sciences at Dartmouth College, Flight Surgeon with NASA, USAF and USN, Navy Chief of Operational Medicine and Navy Radiation Program Manager during Gulf War. Siavash Jabbari is completing residency training in Radiation Oncology at the University of California San Francisco. He received his BSc Degree (Human Biology) from Michigan State University, and his MD from University of Michigan. He has published on quality of life, risk of recurrence, and treatment sequelae in patients with head and neck cancer treated with Intensity Modulated Radiation Therapy (IMRT), and also investigated alternate modes of mechanical ventilation for patients with acute respiratory distress syndrome. He has received many honours and awards including membership in the AOA Medical Honour Society and University of Michigan’s excellence in clinical research award.

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1

Introduction

According to the US National Cancer Institute (OTIR, 2006) “Nanotechnology will change the very foundations of cancer diagnosis, treatment, and prevention”. We have already seen how nanotechnology, an extremely wide and versatile field, can affect many of its composing disciplines in amazingly innovative and unpredictable ways. In fact, nanotechnology and the ideas and methods that it encompasses can be applied to almost any problem that leading researchers face today. Even the most seemingly impossible problems like HIV and cancer become only obstacles in the path to solutions, if we take an imaginative approach. Of course, this is quite logical, since everything around us is made up of atomic and molecular matter, and all of our problems are ultimately rooted in atomic and molecular arrangements. Nanotechnology has at last provided a way for us to rearrange and restructure matter on an atomic scale, allowing us to reach down to the very roots of any problem. Provided that we can thoroughly understand the problem on an atomic scale and develop the know-how to turn our innovative ideas for the perfect solution into reality, we now have all the tools that we need (Mansoori, 2005; Ferrari, 2005; Mansoori and Soelaiman, 2005). The question is what this powerful new interdisciplinary collection of technology and ideas can do to help us find cures for the worst of our diseases? The answer is with nanotechnology, we finally have the ability to understand malfunctions of the most complex biological systems at the atomic and molecular level. As we progress further into our research, the ability to devise progressively more innovative and ingenious atomic-scale solutions and to make them real will allow us to develop amazingly complex and effective weapons against any ailment. However, the field of nanotechnology is still quite young and we are only beginning to understand its capabilities and potentials. The focus of this paper is cancer, which is one of the most widely researched diseases in today’s medical and scientific community. The purpose of this paper is to discuss some of the more recent and innovative solutions that have been made possible by the advent of nanotechnology, and to offer some suggestions for further venues of research.

2

Genetics of cancer

Before we delve fully into the main issue of this report which deals with applications of nanotechnology in cancer prevention, detection and treatment, we must address the underlying causes and the genetic mechanisms involved in cancer. In here we present an over-simplified version of what is known on the genetics of cancer for the sake of brevity. The word cancer was first applied to the disease by Hippocrates (460–370 B.C.), the Greek philosopher, who used the words carcinos and carcinoma to refer to non-ulcer forming and ulcer forming tumours. The words refer to a crab, probably due to the external appearance of cancerous tumours, which have branch-like projections that resemble the claws of a crab. In non-cancerous tissues growth is limited in the sense that cell reproduction is tightly controlled. After a certain number of cells have developed, feedback control (contact inhibition) limits cell division, allowing for tissue repair but not expansion.

but for adult cancers it is generally believed to range from 5 to 15 (Souhami et al. forming tumours in other parts of the body. This kind of a cell cluster is known as a malignant tumour. we can see how even a single nucleotide base inserted (or removed) out of sequence can cause the entire subsequent chain of amino acids. when the tumour grows large enough.. both of these problems must occur in the same cell. and eventually will prove fatal to the patient. The second category is also due to genetic mutations. As stated. 2005). including receptor mediated death. to become permanently disabled (Figure 1).. It must be added that many other mutations can be also cancerous . 2004. 2004. at the same time. Eventually. and causes the apoptosis complex. The first category causes the replication of a cell to become permanently enabled due to a natural or carcinogen-induced genetic mutation.Nanotechnology in cancer prevention. Fu et al. Cancer is a genetically rooted disease that involves the simultaneous occurrence of two general categories of cellular malfunctions. The precise number of genetic changes required for these malfunctions remains unresolved for any cancer.nih. some of the tumour cells can find their way into the bloodstream. in order to cause cancer. This latter phenomenon is known as metastasis. to be incorrect. chromosome translocation or gene amplification (genetic instability). and can severely damage the surrounding tissue as it sucks up essential nutrients and displaces healthy cells. also known as the suicide complex. But. 2005). There are other mechanisms triggering the apoptosis complex. the cells carefully control their divisions using apoptosis complex activated by the p53 tumour suppressor protein. It effectively multiplies the cancer as well as its effects. When this happens in the gene sequence that codes for the protein(s) responsible for apoptosis or damping cell division. which are the building blocks of proteins. the cluster of cells releases chemicals to promote abnormal capillary growth into the tumour. detection and treatment 229 Cancer or neoplasm. which is dependant to chemical messengers. on the other hand. the body has no other option. involves tissues composed of cells that divide and/or grow abnormally.gov/ghr/).. What we present here is a brief introduction to the subject. a cluster of fairly unspecialised cells committed to dividing develops and becomes larger and larger. the cell permanently loses the ability to carry out that particular function (image source: http://ghr.nlm. when both of these mechanisms malfunction. In addition. Fu et al.. especially tumour necrosis factors (Souhami et al. Under normal circumstances. Figure 1 In this illustration. As the uncontrolled cell division continues.

the proteins responsible for division are produced continuously. and the cell continuously divides. controlled by a genetic switch known as an operon (Figures 2 and 3). which is the genetic sequence that codes for the repressor protein itself. If one. preventing the transcription of the genes that are found downstream in the sequence. a mutation occurs in the operator region of the cell division operon. Although in some cases a point mutation may not cause a change in the amino acid sequence. is made up of a sequence of nucleotide bases that collectively code for the production of a myriad of proteins. DNA. and those that are active during cell division. Ali Mansoori et al. the other. or to copy the DNA molecule itself during cell division. which is a group of genes. in a vast majority of cases even the slightest change will render the protein useless . we see that the DNA (deoxyribonucleic acid) molecule is involved in nearly all of them. the ones that are of interest to cancer research are those responsible for reactions that occur during apoptosis. which is the genetic blueprint of the structure and function of every cell. The same DNA is contained inside just about every cell of a particular patient. the presence or absence of a certain substance within the cell causes a repressor protein to bind to the operator region of the complex. If we zoom in further on the genetic processes of the cell. with the only possible differences being the random mutations mentioned above. Others travel to the membrane and imbed themselves there in order to serve as transport channels for various molecules that need to travel into and out of the cell. Out of all these proteins. There are different kinds of operons.230 G. Still others serve to decode the DNA strand in order to produce other proteins. or in the regulator region. thus altering or destroying the functionality of the protein. Figure 2 The shape of a protein is what allows it to fulfill its specific function. Every protein is unique and specially tailored to participate in certain complex biochemical reactions. or both of these mutations occur. Some of these macromolecules serve as catalysts in various biochemical reactions that occur within the cell. and in others a change in the sequence may not cause a change in functionality. In the scenario where we have uncontrolled cell division. thus making it impossible for the repressor to bind. but in general. Each of these groups of proteins is coded for by a gene complex. A difference in the sequence of amino acids that make up a protein results in a difference in shape.

Taken simultaneously. a sequence of genes is turned on by the presence of a specific substance. and can no longer stay bound. Within this population. the transcription of the complex proceeds unhindered. In this case however. every daughter cell contains the precise genetic code of the mother cell. The repressor protein. It is known that greater telomere length is associated with immortalised cell lines such as embryonic stem cells and cancer cells. and which is simultaneously non-responsive to the body’s attempts to eliminate it. which is normally attached to the operator region. When this occurs. Just such a population of cells is known as a malignant tumour or as cancer. Defective proteins made from the mutated sequence can limit or even destroy the cell’s ability to undergo apoptosis. There is a subsequent feedback loop where an excess of the product causes either the same repressor or a complementary repressor to bind to the operator region and prevent further transcription/translation In the scenario where the cell loses its ability to undergo apoptosis. Unusually high levels of telomerase activity are found in cancer cells compared to normal cells. detection and treatment Figure 3 231 In the general model of an operon. The function of telomerase enzyme has been a mystery that’s long baffled cancer researchers. so the problem persists with each subsequent generation of cells. even a single mutation will almost always cause drastic changes in the protein’s structure and function (Figure 2). Because the structure of a protein and its function are directly related to the sequence of amino acids from which it is made. and the proteins that are coded for by the rest of the sequence are made via the transcription/translation process. including the mutations. . and which prevents transcription. is deformed by the substance. these malfunctions result in a cell population that is dividing regardless of chemical signals sent by the body. Telomerase Research has led to identification of an extraordinary enzyme named telomerase that acts on telomeres (the tips of chromosomes) and is thought to be involved in the maintenance of many human cancers. The problem occurs when the mutation is within the sequence that actually codes for the proteins. If the body subsequently tries to eliminate the cell.Nanotechnology in cancer prevention. the mechanism that actually carries out the suicide is out of order. since that would only cause the cell to die prematurely. and the cell does not respond. a defective repressor is not the issue. the mutation can occur in the sequence that codes for proteins responsible for this cell function.

.htm). In this process telomerase adds several repeated DNA sequences to telomere and then separates. Ali Mansoori et al. while telomerase is an enzyme. a second enzyme named ‘DNA Polymerase’ helps to attach the complementary strand of DNA.232 G. A telomere is a repeating sequence of double-stranded DNA located at the ends of chromosomes. The presence of telomerase in various human cancers and its absence in many normal cells indicate it to be a good target for anticancer drugs and useful for cancer diagnostics. RNA template is used for the attachment of a new strand of DNA. 1997). the famous medical/scientific illustrator. 1994. Telomerase is the catalyst for increasing the length of telomeres by helping to add on telomere the appropriate repeating sequences of DNA. It is likely that if cancer cells made telomerase. Shay and Bacchetti. It is believed telomerase switches on cancer cells and is key to the spread of the majority of cancers (Figure 4). 1996). they would retain their telomeres and would potentially survive. Figure 4 Illustrations of telomere. This completes the double stranded extension of the chromosome ends .com/html/folio/MA-Winslow. as will be discussed later in this report (Greider and Blackburn. telomerase and their functions by Terese Winslow (http://iv-stock. At the next stage. Right panel show telomerase binds to the ends of the telomere via an RNA template. The telomeres progressively shorten as cells divide and differentiate as per their normal lifespan (Kim et al.

it requires time and monetary investments to develop such treatment methods in short time. called sunscreen. Even so. in turn. genetic mutations are caused by artificial or natural carcinogens only some of the time. With present science and technology there is very little we can do to prevent this from happening. . Most apparently. to coat our skin prior to prolonged exposure to sunlight. they are indeed possible. We use this emulsion. It is here that nanotechnology can play a pivotal role. they may occur spontaneously during DNA replication and cell division. But most patients do not recognise the problem until it has actually occurred. is caused primarily by ultraviolet radiation from the Sun (Figure 5). we are interested in methods involving nanotechnology that are entirely novel and thus unparalleled by anything that has been explored previously. However. Unfortunately. However. we shall now look at some of the progressive treatment options. therapeutics. is there a way to eliminate cancer through nanotechnology before it starts? Although there is little current research on preventive treatments using nanotechnology. let us consider melanoma for example. detection and treatment 233 Armed with a basic understanding of the underlying causes of cancer. The current method of preventive treatment against bombardment with this kind of harmful radiation involves suspending a substance that either absorbs or scatters ultraviolet radiation in a thick emulsion. we shall look at the currently-available methods. nanotechnology-based treatments are no more challenging to devise than the currently used disease-time treatment methods. In cancer. Some of the problems with this method are that this emulsion can be easily rubbed off and can loose its effectiveness over time. if genetic mutations are the underlying cause. Melanoma. and see if nanotechnology can be used to make them safer and more effective. scientists lack the technological innovations to turn promising molecular discoveries into benefits for cancer patients. creates new opportunities to attack the molecular underpinnings of cancer. then we must counteract the causes of the mutations. thus needing to be reapplied periodically. which. a form of skin cancer. which makes preventive medicine a rarely utilised. and preventives to keep pace with today’s explosion in knowledge. 3 Nanotechnology preventive approach In general. 2006) Specifically. In addition.Nanotechnology in cancer prevention. one can easily see why the proposed nanotechnology alternatives to current preventive treatments have so strongly attracted the attention of the scientific and medical communities in recent years. To demonstrate the viability of the nanotechnology-based treatments.” (OTIR. At other times. Nonetheless. the best way to eliminate a problem is to eliminate the cause. in all other cases. The vast knowledge of cancer genomics and proteomics emerging as a result of the Human Genome Project is providing critically important details of how cancer develops. In fact. the problem can be perceived differently at various stages of the disease. After a careful review of the most advanced disease-time nanoscale treatment methods. providing the technological power and tools that will enable those developing new diagnostics. eliminating the carcinogens is indeed a highly effective way of cancer prevention. although a highly effective form of cancer prevention. According to the US National Cancer Institute (OTIR): “The advent of nanotechnology in cancer research couldn’t have come at a more opportune time.

Figure 5 UV radiation is one of the most prominent causes of DNA damage. An even bigger problem is that we leave openings in the sunscreen coating during sunscreen application due to macro-scale and micro-scale imperfections in our skin. The result a mutated genetic sequence and the production of defective proteins Source: http://earthobservatory. However. Individual nucleotide bases readily absorb UV radiation and can become excited after even short-term exposure. the toxicity of the substance that is used. The most important issue to consider in this form of treatment is. Nanoparticles attached to desired drugs or substances can be conjugated to short peptide chains. This allows the Ultra Violet (UV) radiation to permeate through the dead layer of skin. or UV absorbing substances like octyl methoxycinnamate and oxybenzone (Figure 6). Of course. If the cells can be coated directly. spreading out to a wider area due to slit diffraction and causing more widespread damage. and sometimes even the covalent bonds between the phosphate backbone and the ribose to break. This can cause hydrogen bonds between the two complementary chains. we can effectively coat these cells with sunscreen on the nanoscale. With this nanotechnology-based preventive treatment method.nasa. Ali Mansoori et al.234 G. causing genetic mutations. If we manufacture nanoparticles attached to UV scattering substances like zinc oxide (ZnO) and titanium oxide (TiO2). proteins or artificial nanobodies. and specifically target these nanoparticles to skin cell surface proteins. The biochemical effects of a substance on the patient’s health must be thoroughly evaluated by standard laboratory testing procedures as well as clinical trials before this treatment can be safely implemented. if this method can indeed be turned into reality. 1996). this is a purely theoretical suggestion. Since UV radiation is high frequency and thus high energy. we would effectively eliminate most of the problems mentioned above. which is based on works that are unrelated to skin cells. All of these problems take away from the overall effectiveness of this preventive method. the obvious result will be a large reduction in the incident of melanoma due to the sun’s radiation. . the problem of diffraction in case where an area is sparsely coated will be eliminated. It is proposed simply as an example of the potential application of nanotechnology.gov/Library/UVB/Images/ dna_mutation. it can easily damage the delicate DNA double helix. of course.gif Some very recent works have shown that it is possible to tag specific types of cells with nanoparticles by conjugating them to targeting agents designed to recognise cell-specific surface proteins (Greider and Blackburn.

there are several ways to view the problem. and simply flooding the entire body with it causes system-wide damage and serious side effects.Nanotechnology in cancer prevention. but taken constantly in large doses they can also be very damaging to the overall health of the patient. but the idea remains the same. 1989). Taken together. detection and treatment Figure 6 Ultraviolet radiation absorbing organic substances 235 We now have the ability to quickly and easily map large proteins and model them in three-dimensional space (Gupta et al. Almost everyone has heard of or seen chemotherapy patients who have lost their hair. This method actually dates back to the mid-17th century. with similar results. Thus. these drugs can be effective. A currently popular treatment for AIDS is a drug cocktail. The most significant recent breakthroughs have been made in this area. A relatively long-standing strategy dating back to the 1950s is to flood the body with substances that are especially toxic to tumour cells. 2005). 4 Nanotechnology approaches for cancerous cell destruction Preventive treatments are not much good to those who have already developed the disease. each somewhat effective against the disease. then the obvious strategy is to remove or to destroy them. The most commonly used Hepatitis C treatment is as severe. electronic cloud distributions (Aquilanti et al. or a combination of several different drugs. or the cells that make up the tumour and end their pararcine signalling effect. these techniques give us all that we need in order to specifically target any type of animal cell. 2004). Again. it is no wonder that a majority of innovative treatments are focused here. as well as extensive knowledge of atomic and molecular interactions (Rafii-Tabar and Mansoori.. Administered together. the method discussed above is but one example of many possible applications of the fascinating new nanotechnology known as nanobiotechnology. We also have the ability to sequence and manufacture nucleic acid and peptide chains quite easily (Lebl and Hachmann. . If we see the cancerous cells of the tumour as the causing agents of the disease. Unfortunately. a Scottish surgeon first suggested the surgical removal of the tumour (Denmeade and Isaacs. 2002). The traditional approach is to simply eliminate the causing agents. or developed other serious disorders.. lost significant weight. Of course. we have also taken similar approaches to treating other seemingly incurable diseases such as AIDS and Hepatitis C. And since these are the people who require the most immediate medical help. A drug that is especially toxic to tumour cells is usually also toxic to healthy cells. 2001). It is a common problem and in fact. we have made great progress in the last 350 years. tumour cells are not dissimilar enough from healthy cells to distinguish one from the other using such large-scale techniques. when John Hunter. provided that it can be distinguished from other cell types by the presence of at least one cell-specific surface protein.

insomnia. with the highest success rates ranging only from 25% to 75%. although concentrating the drug in the desired area. Two of the major drugs used to treat these diseases are Inteleukin-2 and Interferon. and hair loss. irritability. The nanoparticle method is simply the next step in the process of finding an effective way of administering Paclitaxel. This method was found to be somewhat ineffective. headaches. both. and flu-like symptoms. While some patients are highly resistant and are lucky enough to get through the treatment with mild to moderate depression. due to the drug’s low water solubility. pains. as sufficient concentrations of the drug in and around the tumour were difficult to achieve without raising the toxicity to an intolerable level. Some recent works have explored cancer treatments from nanotechnology perspectives. thus not allowing the bulk to come into direct contact with the tumour cells and produce the desired effect.. AIDS and Hepatitis C as well as many other problematic conditions that currently have the medical community perplexed and frustrated (Gougerot-Pocidalo et al. We shall discuss three of them here: • The first method involves nanoparticles loaded with Paclitaxel (Figure 7). eye problems. there is a pressing need for newer and more effective forms of treatment. Pyrhönen et al. and is therefore relevant to consider research for actual in vivo treatment of prostate cancer in human patients. loss of appetite. The research was conducted on living mice. A solution to this problem was later developed in the form of Cremophore EL. Ali Mansoori et al. This was done partly to minimise the uptake of the spheres by macrophages and partly to improve the comparison of the effectiveness of this new treatment with Cremophor EL. to list just a few (Gougerot-Pocidalo et al. These alone have some experts furrowing their eyebrows. stomach and digestive tract problems. While the subsequent discussion addresses research of treatments specific to cancer. 1999).. This shows that even unconjugated nanoparticles are as effective as Crempophor EL. 2004) took a similar approach to administering the drug preparation. The frequent dosing that was required to maintain sufficient concentration again caused nonspecific toxicity.236 G. which aside from these problems has a wide range of effective anti-cancer activity. nanotechnology does have the capability to deal with. With such poor results. This research compared the efficacy of Paclitaxel-loaded nanopartlicles to Cremophore EL. now in the vicinity of the tumour. Paclitaxel was originally used by simply flooding the system via the bloodstream. 1994. but in addition. severe aches. although about the same as those treated with unconjugated nanoparticles. This method gave results that were only slightly better because the gel.. Yet the biggest setback is that these treatments are effective only some of the time.. A select few are actually driven to suicide or homicide during or immediately after treatment. 1994. a currently used colloidal suspension of the drug. In their work researchers (Sahoo et al.. a common agent used to treat prostate cancer (Sahoo et al. others are plagued with severe depression. was too thick to allow easy diffusion of the drug. heart problems. paranoia. while those that are also conjugated for targeting . and even suicidal and homicidal tendencies. and some but not all of the side effects include a weakened immune system. in that they also injected the nanoparticle preparation into the tumour. The results indicated the survival rates of the mice treated with the Cremophor EL suspension were much lower than those treated with conjugated nanoparticles. Pyrhönen et al. 1999). which was a suspension of the drug in a thick gel designed to be injected directly into the tumour. 2004). many of these treatments have varying levels of psychological effects..

The underlying principle is that these particles readily absorb laser radiation and convert it to heat.. 2004). For the microparticle run. Thus. Each type of sphere was conjugated to recognise the CD8+ protein imbedded within the cell membranes. 1999) for different nanoparticle sizes as shown in Figure 8. further research will likely yield tumour-specific recognition ligands. as mentioned in the preventive treatment section. The effectiveness of the gold nanosphere method was gauged by analysing uptake of propidium iodide (C27H34N4I2. determine patient-specific/tumour-specific proteins. • A second potential treatment involves absorption of light by gold nanoparticles (Pitsillides et al. A microsphere run was carried out in order to allow observation under a light microscope as well as to compare its effectiveness to the nanosphere run. Experience has shown that as we become progressively more skilled at identifying and modelling proteins. They also have distinct absorption peaks in between ~500–600 nm wavelength electromagnetic radiation (Link and El-Sayed. During the microscale experiment. This fluorescent dye was allowed to penetrate into the cytoplasm. we may be able to draw some blood from the patient. tumour growth. One of the main conclusions to be drawn from these results is that conjugation of nanospheres (spherical nanoparticles) with targeting moieties greatly increases the effectiveness of a treatment. The duration of the pulses for the nanoparticle run was kept under 10 ns. To achieve the desired results. was used to distinguish cells among the general population of lymphocytes under study (Pitsillides et al. The cells were then conjugated to both kinds of particles and the population labelled with latex microspheres was analysed by a fluorescence microscope. embedded in nanoparticles. which will allow us to tailor treatments to specific kinds of cancer.. A few days later. During the first stage. a cell surface protein. which was also monitored. which are conjugated to artificial ligands ready to target the exact proteins that are specific to that patient. The cells under study were first labelled with a general fluorescent dye that was non-cell-specific.Nanotechnology in cancer prevention. To distinguish between CD8+ and regular lymphocytes under a fluorescence microscope. Furthermore. the duration was kept under 1 µs. Gold nanoparticles are frequently used in electron microscopy due to their high electron density. was actually reversed with the use of conjugated nanoparticles at 24 mg/kg for the period of observation (Sahoo et al. and send the data away to a lab. one may use commercially available gold nanoparticles and conjugate them to certain recognition molecules engineered to target CD8+ lymphocyte cells. a fluorescent dye (R-phycoerythrin) conjugated to anti-CD8 IgG antibodies was used. Any further research should be directed primarily in this area. Perhaps in the not so distant future. the cells were briefly irradiated with a 532 nm or 565 nm laser. CD8. 2003). detection and treatment 237 produce much better success rates. CAS: 25535-16-4) and subsequently measuring FITC fluorescence. The observations showed an interesting phenomenon known as . 2003). we also become better able to create artificial recognition molecules to effectively target these proteins. The method involves gold-coated nanoparticles conjugated to recognition ligands. Iron-oxide doped latex microspheres were also used in a concurrent study. a drug will be prepared that is highly effective against that specific type of cancer. The experiment consisted of two stages. the frame-grabber was used to record an image of the field approximately 100 ns after irradiation..

It involves using small magnetic particles that respond to an externally applied magnetic field by heating up.238 G. Cavitation is caused by the rapid temperature increase. The study was the first to use nanosised particles to achieve hyperthermic conditions and has managed to prove the method to be quite effective. this technique deserved extra attention from prospective researchers. nanoparticles were used to coat the tumour cells. 2003) have successfully applied this technology to biological systems in vivo. cavitation due to phase transition.. It is hypothesised that the relatively old concept of hyperthermia can be combined with methods in nanotechnology to achieve previously unequalled positive results. Particle fragments have been observed which support this phenomena (Pitsillides et al.. 2003).. As one of the leading applications of nanoparticles. Theoretical calculations of the temperature distribution in and around the spheres were carried out using the Goldenberg and Tranter heat transfer model (Goldenberg and Tranter.. 1952) assuming uniformly heated homogeneous spheres embedded in an infinite homogeneous medium. • Finally. The mice were treated for 30 minutes at a steady intratumoural temperature of 47ºC. As the bubble grows in volume. This study was done in vivo with murine mammary carcinoma cells transplanted in the hind leg of mice. and is scheduled to enter clinical trials in humans in the near future (Farokhzad et al. In humans. An added effect of these changes is the lowered resistance of cells to radiation damage. When appropriate numerical values for radiation rate. Magnetic fluid hyperthermia is a method for cancer treatment that has been around for nearly 50 years. Ali Mansoori et al. Hirsch et al.. 2001). 2001. A study done on mice has recently shown to be just as effective in leading to complete remission and elimination of malignant tumours. The impact can be so violent that for smaller particles. The conclusions to be drawn from this study are that light-responsive nanoparticles are potent tools for nanosurgery and cancer treatment. which were then . In fact. some current investigations (Loo et al. the hyperthermic temperature range falls between 41ºC and 46ºC. Hyperthermia is a biological term used to describe the phenomenon that occurs when living cells or tissues are heated to temperatures slightly above the highest that can occur naturally. They are highly effective cell-destruction agents that can be targeted quite effectively at specific cell types by the use of the appropriate recognition molecules. This phenomena is believed to be the mechanism of cell destruction and responsible for the subsequently observed cell death. which causes the water in the immediate vicinity of the particle to vapourise and to form a bubble as the vapour pressure overcomes the surface tension of the liquid. almost irreversible cell damage can result. the third nanoparticle method for direct cell destruction to be discussed is the magnetic nanoparticle hyperthermia method (Jordan et al. In the study. 1999). Cell death was confirmed by the leaking out of the fluorescent dye due to lacerated cell membranes. radius and conductivities are inserted in the model the researchers found that irradiation of the spheres caused a rapid increase in temperature of the order of thousands of degrees Kelvin which is the reason for sudden formation of bubble and its rapid growth. it cannot sustain itself and collapses inward. When human cells are briefly brought into this temperature range. it can cause fragmentation.

making prospective conjugation to recognition ligands a necessity. Figure 7 Chemical structure of Paclitaxel. a common chemotherapeutic agent used to treat some cancers. 48 and 99 nm diameter gold nanoparticles Source: Link and El-Sayed (1999) . are strongly adhesive to human colon adenocarcinoma cells. An added benefit is that cells that have picked up some of the particles cannot get rid of them. However. thus opening up the prospect of treating types of cancer that involve deep-seated tissues and organs. 2001). 2001) was not yet readily available. It is isolated from the Pacific yew tree (Taxus brevifolia) Figure 8 UV–visible absorption spectra for 9. which consist of aminosilan shell magnetite with a core diameter of about 10 nm. every daughter cell will have one half of the amount of particles present on the mother cell. It acts by promoting and stabilising the polymerisation of microtubules. detection and treatment 239 subjected to magnetic fields from 50 kHz to 100 kHz using a prototype AC magnetic field applicator. and thus. this effect is either far decreased or not observed at all with other kinds of cells. with all of the recent advances in the production of artificial antibodies and other recognition ligands.. One benefit of using this method is that it can be applied internally. 22.Nanotechnology in cancer prevention. this method could be greatly improved by targeting the particles to specific types of cells (Johannsen et al. However. there is a possibility of re-treatments. When this study was done. conjugation nanotechnology (Santra and Tan. The particles. If the initial concentration of the particles is sufficiently high.

2003). basic anatomy and biology tell us that cells within the human body get a vast majority of their nutrients and energy from the bloodstream. Numerous studies have explored the possibility of isolating cancer tumours from the bloodstream. and can be applied to other fields as well. A general nanoparticle consists of a core that can have a constitution ranging from very simple to highly complex. Also imbedded in the core were integrin-antagonist lipids. The study used nanoparticles specifically designed to target cells that make up these freshly created capillaries by delivering to them ATPm-RAF. energy and entropy inputs. Therefore. which gave the outer surface of the particle a net negative charge. the most current disease-time nanotechnology-based treatment methods involve the use of some type of nanoparticle. Furthermore. and whose heads served as the targeting moieties for the epithelial cells. our goal is to separate the tumour from the circulation in order to kill it. outputs and accumulations. 6 Nanoparticle science and technology Clearly. these concepts are quite general. the combination of which stimulates the development of new capillaries that grow into the tumour (Figure 9). we can limit the outputs. The tumour cells underwent necrosis and were eliminated shortly thereafter. The general principles of mass balance. a brief description of bio-medical nanoparticles is in order. Cells that are cut off from circulation quickly undergo necrosis and are effectively eliminated. Thus. Since our ultimate goal is to destroy the tumour. energy conservation and entropy production are applicable to bio systems as well as industrial processes.240 G. The nanoparticles consisted of a core of phospholipids. or pre-synthesised RNA (ribonucleic acid) strands responsible for inducing apoptosis. cutting off the tumour from circulation and preventing further growth. As a result of intravenous treatment with these nanoparticles in live mice. as well as permeation and visibility enhancers. whose tails were identical to the phospholipids tails. which are necessary for the tumour cells to get rid of toxic waste products that are left over from the multitude of biochemical reactions continuously taking place. we can define the malignant tumour as our bio system and proceed to investigate the mass. . we realise that this can be achieved by limiting or eliminating the inputs of the needed nutrients and the useful energy that are vital to its growth and survival. Mass and energy balance are well understood and are widely used in all types of science and engineering. such as medicine. 5 Physics and engineering concepts in cancer treatment Aside from destroying cells directly. The surface may be bare or conjugated to targeting ligands. Furthermore. The charge allowed for facilitated conjugation of any desired DNA or RNA sequence to the particle’s surface. the newly formed capillaries were destroyed.. with the hydrophobic tails directed inward. The core can contain one or several payload drugs. Ali Mansoori et al. The underlying principle of the study is that the cells within the growing tumour produce and send out basic Fibroblast Growth Factor (bFGF) accompanied by Vascular Endothelial Growth Factor (VEGF). depending on the intended application. we can take a more elegant approach to tumour elimination. Likewise. One that is exemplary will be discussed here (Reynolds et al. and likewise use the bloodstream to eliminate the toxins. Therefore.

Mehvar. 1985). as discussed below.nci. iron oxide.. titanium oxide. called receptors.htm Figure 10 An antibody (also called an immunoglobulin) is a protein that is manufactured by lymphocytes (a type of white blood cell) to neutralise an antigen or foreign protein (Mansoori. The binding of either VEGF or bFGF to its appropriate receptor activates a series of relay proteins that transmit a signal into the nucleus of the endothelial cells. 2000) to prevent macrophage uptake of the nanoparticle. 2005.nih.Nanotechnology in cancer prevention. 1959) or polyethylene glycol ligands (Figure 11) (Tabata et al. sitting on the outer surface of the cells. In addition to nanoparticles made of gold. Monoclonal antibodies. Figure 9 In this figure VEGF (vascular endothelial growth factor) and bFGF (Basic fibroblast growth factor) are first synthesised inside tumour cells and then secreted into the surrounding tissue. a special type of antibody designed in the laboratory.. and zinc oxide other nanostructures. hold promise for novel nanotechnology-based cancer treatments. 1981. Galfre and Milstein. they bind to specific proteins. When they encounter endothelial cells that line the interior surface of blood vessels. Evan et al. 1997. The nuclear signal ultimately prompts a group of genes to make products needed for new endothelial cell growth Source: Figure and statement is from: http://rex. detection and treatment 241 like antibody (Figure 10) (Singer.gov/behindthenews/ uangio/13uangio/13uangio. which can guide nanoparticle medications directly to the cancer cell .

2001). Fullerene as a nanoparticle has found various applications in cancer treatment (Moghimi et al. Tabata et al. In another study (Tabata et al. breaking the balls requires temperatures of over 1000°C.. C76. but some other relatively common ones are C70. Fullerenes are large carbon-cage molecules. Fullerenes are small compared to many organic molecules such as proteins.5 nm in diameter. 2000). . of course. 1997). and C84. Andrievsky and Burenin. they are quite stable.. also called a ‘buckyball’. refer to the number of carbon atoms that can be found in the structure. The subscripts. By far the most common one is C60. 1997) the photodynamic effect of PEG-modified fullerene on tumours was studied. fullerenes will ‘sublime’. Fullerene cages are about 0. usually monomethoxy PEG [CH3 (–O–CH2–CH2)n–OH] is first activated by means of an activating agent (linker) before the addition of the particle Source: Delgado et al.242 G. For coupling proteins to PEG. At much lower temperatures (a few 100°C). As an example the preventive and medicinal action of Hydrated Fullerene (HyFn) as shown in Figure 12 has been investigated (Andrievsky and Burenin. (1992) 6.7–1. drug or protein carrier (Mehvar. 2001). Figure 11 Polyethylene glycol (PEG) as ligand. 2001..1 Fullerenes Fullerenes are quite stable molecules and their stability makes them good candidates for safely delivering highly toxic substances to tumours (Moghimi et al.. 2001. Chemically. With chemical formula (–CH2CH2O–)n. which means vapour will form directly from the solid. Ali Mansoori et al. (MW ≤ 10 kD) PEG is very attractive as nanoparticle.

2001.Acceptor Complex of H-bonded Water Molecules with C60.. (2001). Figure 13 Schematics of a functionalised single-walled carbon nanotube with Cyanine Dye #3 Labelled DNA (Cy3-DNA) Source: Kam et al. as various experimental techniques have revealed that covalent bonds formed between polymer radicals and acid-treated carbon nanotubes (Chen et al. 2001. In Figure 13 schematics of a functionalised single-walled carbon nanotube with Cyanine Dye #3 Labelled DNA (Cy3-DNA) as reported by Kam et al.2 Carbon nanotubes Different kinds of carbon nanotubes (CNTs) have different properties. When exposed to near-infrared light. Kam et al. To achieve the attachment of nanotubes to proteins. Multi-walled carbon nanotubes (MWNTs) can bind with proteins. The first is the state of dispersion of the CNT in the solution and the second is the interfacial adhesion between the CNT and the protein. carbon nanotubes quickly release excess energy as heat (~70°C). 2001). Donor. whereas normal cells are not. two issues must be considered... which can kill cancer cells. detection and treatment 243 Figure 12 Hydrated Fullerene (HyFn): Supramolecular. It is assumed that mechanisms of HyFn medicinal actions are connected with their highly universal positive influence on biological processes Source: Picture is from Andrievsky and Burenin (2001) 6. Carbon nanotubes (Chen et al. 2001) possess interesting property of adsorbing materials on their surface and heating up upon absorbing near-infrared light wave. This is how carbon nanotubes target to cancer cells. In one study (Kam et al... 2001) it is shown that cancer cells tend to be coated with folate receptors. (2001) . During therapy of oncological states by Hydrated Fullerenes the prognosticated life expectancy (PLE) was increased in more than 1. Teker et al.5–2 times.Nanotechnology in cancer prevention.

(2001) have shown that single-walled carbon nanotubes are molecular transporters or carriers with very high optical absorbance in the 700–1100 nm near-infrared (NIR) light where biological systems are transparent In this special spectral window single-walled carbon nanotubes (SWNTs) have strong optical absorbance which is used for optical stimulation of nanotubes inside living cells.. Continuous NIR radiation can cause cell death because of excessive local heating of SWNT in vitro. Modification in their size and structure exhibit many colours in the entire ultraviolet-visible spectrum (Figure 15) Quantum dots are photoluminescent with a wide absorption spectrum and a narrow emission peak (Figure 15). 1993. which can be precisely controlled. 2001.3 Quantum dots A quantum dot is a semiconductor nanocrystal with a diameter of a few nanometers (Figure 14). Size-tunable light emission. Ali Mansoori et al. biological labelling and diagnostics (Murray et al. .. Thus. without harming receptor-free normal cells. Bioconjugated quantum dots have produced new possibilities for multiplexed and ultrasensitive imaging of biomolecular targets in animal cells. Figure 14 Semiconductor nanosise crystalline quantum dots possess quantised energy levels with unique optical and electronic properties. on the order of the electrons’ de Broglie wavelength with varied sizes and shapes. Because of its small size it behaves like a potential well that confines electrons in three dimensions to a region on the order of the electrons’ de Broglie wavelength in size. Gao et al. Their immense photo-stability aids in the ability to track cell processes for extended periods of time and to give more insight on intermolecular relationships. selective internalisation of SWNTs inside cells labelled with folate receptor tumour markers. Quantum dots photoluminescence is used in bio-imaging. the transporting capabilities of carbon nanotubes combined with suitable functionalisation chemistry and their intrinsic optical properties can lead to new classes of novel nanomaterials for drug delivery and cancer therapy. Kam et al. improved signal brightness. containing anything from a single electron to a set of hundreds or even thousands of electrons. and NIR-triggered cell death. They confine electrons in three dimensions to a region. 6. 2004). Selective cancer cell destruction can be achieved by functionalisation of SWNT with a folate moiety.244 G. resistance against photobleaching and simultaneous excitation of multiple fluorescence colours are some of the unique optical and electronic properties of quantum dots.

1995) in the solid state. Current applications are focused on in vitro applications such as: • • cell and cell organelle detection and separation immobilisation. Magnetic nanoparticles were first discovered in a biological organism (chitons) in 1962 (Lowenstam. 6.. 1962).5 nm size manufactured by Evident Technologies: www... Bakalova et al. Nanoscale magnetic particles with a variety of compositions. which do not retain magnetism when removed from a magnetic field (Moffat et al. isolation and determination of biologically active compounds.. . Several applications for these materials exist.com 245 The semiconductor material used in quantum dots is potentially toxic to the cells and humans. as ferrofluids (Raj et al.Nanotechnology in cancer prevention. However. Polymer-encapsulated quantum dots are nontoxic for in vivo use. 2004). Tartaj et al. their long-term in vivo toxicity and degradation need further study. primarily in the biomedical and magnetic recording industries.evidenttech. 2003).4 Magnetic nanoparticles The magnetic effect of magnetic nanoparticles is due to superparamagnetic iron oxides (SPIO) core(s). typically Fe2O3 and Fe3O4. detection and treatment Figure 15 A Typical UV–visible absorption and emission spectra for quantum dots. Numerous current and potential commercial biomedical applications exist for systems comprised of magnetic nanoparticles. (Figure 16). sizes and stabilisers have been prepared in the past four decades. The first excitation peak is at the 1550 nm wavelength and the emission peak is at 1630 nm. The iron oxide core(s) surrounded by a silicon coat or a layer of polymer such as dextran or polyacrylamide. This data is for PbSe QD nanocrystals of ~5. Much more research still needs to be done to achieve reproducible and robust surface functionalisation and to develop flexible bioconjugation techniques for the use of quantum dots (Medintz et al. 2001. 2001..

Their polymer coating prevents their cytotoxicity and allows them to move freely in the organism without adhesion or reaction Magnetic nanoparticles are also noteworthy for in vivo diagnostic purposes. They are manufactured to enclose medications for drug delivery like chemotherapy (Basu and Basu. Figure 16 Structure of a SuperParamagnetic Iron Oxide (SPIO) Poly Acrylamide Magnetic (PAM) nanoparticle (Moffat et al. Torchilin and Weissig. 2003.5 Liposomes Liposomes consist of synthetic microscopic fat globules of lipids (Figure 17). and hold them until treatment is finished. 2001). Magnetic nanoparticles can be used to target drug delivery.. . 6. Their paramagnetic characteristics have made them good candidates for in vivo cancer cell destruction through hyperthermia. They have applications in magnetic immunoassay and also as Magnetic Resonance Imaging (MRI) contrasts. 2001. Liposome therapy is a well-developed technology for delivery of chemotherapy drugs (Silva et al. They are nanoscale closed vesicles consisting of a single lipid bilayer.246 G. 2002).. 1999). Their sizes are in the range of 50–300 nm.. Magnetic nanoparticles are sensitive to magnetic fields and electromagnetic radiation.. which are incredibly biodegradable. as hyperthermia agents to destroy cancer cells and have potential to move the particles to specific sites in an organism. By this process drug toxicity to healthy cells is decreased and its efficacy may be increased. This property induces hyperthermia for cancer treatment (Jordan et al. Duncan et al. The fatty layer on liposome confines and protects the enclosed drug until the liposome is delivered and adheres to the outer membrane of target cancer cells. 2005). Ali Mansoori et al.

which provides new unique properties that could be applied within the emerging field of nanotechnology (Zhang et al.) to tissues and into cells Source: Mansoori (2005) 6.6 Dendrimers Dendrimers are unique macromolecules that have applications in developing strategies for nano-scale globular shapes with small cores. DNA/PAMAM (Polyamidoamine) dendrimer complex is used for DNA delivery to cell nucleus due to its high transfection efficiency and very low toxicity. 2003). These nano objects have gained interest because of their cylindrical structure. Dendrimers (Figure 18). generally possess multiple branches which can be used to carry a variety of agents fulfilling various functions at once.Nanotechnology in cancer prevention. which is used to carry a DNA molecule and (b) Format of DNA wraps around the dendronised polymer resulting in 40Å pitch (single helix characterised by the height per turn) (a) . Figure 18 (a) An example of a dendrimer used to carry a variety of agents fulfilling various functions. etc. The thickness of the polymers is in the range of several nanometers. detection and treatment 247 Figure 17 Cross section of a liposome: a synthetic lipid bilayer vesicle that fuses with the outer cell membrane and is used to transport small molecules (drug. Chemical structure and formation of a Poly-amidoamine (PMAMA) dendrimer nano-cylinder (dendronised polymer). Dendronised polymers are cylindrical macromolecules that are composed of a linear polymeric backbone and dendritic side chains (Figure 18). For example..

248 G. Figure 19 Low molecular weight diamondoids Source: Mansoori (2005) and Ramezani and Mansoori (2006) The smallest diamondoid molecule is named adamantine.. Figure 18 (a) An example of a dendrimer used to carry a variety of agents fulfilling various functions. 2000) and have found many medicinal applications including for cancer treatment. Ramezani and Mansoori.7 Diamondoids Diamondoids are cage hydrocarbons with little adverse health risks. 2001). good water solubility. 2005. Ali Mansoori et al... which is used to carry a DNA molecule and (b) Format of DNA wraps around the dendronised polymer resulting in 40Å pitch (single helix characterised by the height per turn) (continued) (b) Source: These figures are from Nikakhtar et al. (2005) Poly-amidoamine (PAMAM) dendrimers are favourite candidates for use as the backbone of multitasking therapeutics because of their well-defined surface functionality. 6. it has been proven that . 2001). 2006). For example. low polydispersity and their lack of immunogenicity (Choi et al. Chemical structure and formation of a Poly-amidoamine (PMAMA) dendrimer nano-cylinder (dendronised polymer). For example. Extensive amount of investigations have been performed related to synthesis of new diamondoid derivatives with better therapeutic actions and less adverse effects. 2002) in the design of new dendrimers with preferred molecular functionalities. There are many ongoing research activities (Fréchet and Tomalia. good therapeutic effects and many useful derivatives (Figure 19) (Mansoori. the controlled surface modification followed by conjugation of folate and fluorescein moieties on the surface of a dendrimer is shown to yield molecules capable of targeting to tumour cells through folate receptors (Quintana et al. Adamantane derivatives are readily synthesised (Orzeszko et al.

Also dimethyladamantylmaleimide has been effective for growth inhibition of human colon cancer (Wang et al. and detection is made possible by measuring the conductance in real time (Zheng et al. The array is submerged in a biofluid where the molecules that are present are allowed to bind to the antibodies. 2005). TNF is referred to a substance that can improve the body’s natural response to cancer by killing the cancer cells. even with concentrations in the range of parts per million. There are currently two equally effective nanoarray methods.. detection and treatment 249 adamantylamino-pyrimidines and -pyridines are strong stimulants of tumour necrosis factor-Į (TNF-Į) (Kazimierczuk et al. which is used as an anti-cancer agent. in vitro detection studies have recently produced some impressive breakthroughs (Jain. .. Another example is 1. 2000). Although in vivo detection is still a challenge. The second method involves a nanoarray of Atomic Force Microscope (AFM) cantilevers which are equipped with antibodies specific to selected molecules. As they bind. Each nanowire is designed to be a good binding site for a specific biomolecule.. is an example (Reissmann et al. and the deflection is measured by a combination of a highly focused laser beam and sensitive photodetectors. The bradykinin antagonist. with a technique similar to that used in AFM. Two approaches to cancer detection may be envisioned and they include • • in vitro (laboratory-based) diagnostics in vivo diagnostics. 1991) which possesses an antitumour and antibacterial activity. they cause the levers to deflect.Nanotechnology in cancer prevention. For example. we can now detect multiple biomolecular markers at very low concentrations in various biological fluids. with the use of some recent discoveries in nanoarrays. The biofluid under study is passed through a channel where it is allowed to come into direct contact with the wire array.. In order to provide early and thus more effective cancer treatment. Any discoveries that are made in this area will surely benefit fields other than medicine and cancer research. Nanoparticles already have a multitude of applications and will likely have many more in the near future. A wise course of action would be to direct our collective research and development efforts into improving and expanding nanoparticle science. early detection of the disease is crucial. 7. The first method involves nanowires (Figure 20) connected to a high-sensitivity electronic ammeter. 2001). 7 Detection and diagnosis through nanotechnology Another important issue to be addressed is cancer diagnosis through nanotechnology. Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. Both methods can yield data that are highly accurate.1 In vitro (laboratory-based) diagnostics Laboratory-based (in vitro) nanotechnology methods are based on the concept of computer chips.. The conductance of the wires changes as the molecules bind. 2005).6 -diaminodiamantane (Malik et al. and should therefore be designated as an interdisciplinary goal. 2001).

Ferrari (2005) suggests more novel measuring methods must be developed that are dependent on other physical properties.. cytosine or thymine . This problem has been in the way of effective in vivo detection for quite some time. the units from which DNA molecules are constructed. (Middle) A solution containing telomerase is delivered to the device array. each carrying a single nitrogenous base. However. Figure 20 Schematic of the telomerase binding and activity assay as proposed by Zheng et al. and from which the biofouling signal can be decoupled using appropriate mathematical algorithms. (Bottom) Subsequent addition of dNTPs leads to telomerase-catalysed primer extension/elongation which can be detected (Zheng et al. (Top) Silicon-nanowire devices modified with oligonucleotide primer. Since serum proteins are present in healthy as well as malignant environments. Another method is to implant biosensors directly into the patient and to have them relay gathered information to an external data collector. 2005). significantly higher concentrations of the desired molecules are necessary for accurate detection. (2005). the accuracy of the measurements can be greatly impaired. due to conditions that are much more adverse in a living patient. guanine. 7. Ali Mansoori et al. The major problem with these methods that still remains unresolved is biofouling. and telomerase binds in a concentration-dependent process.250 G. The abbreviation ‘dNTPs’ stands for Deoxynucleotide-triphosphates.2 In vivo diagnostics Some promising in vivo techniques are currently under development. One method is to use nanoarrays similar to those described above. They include adenine. or the nonspecific adoption of serum proteins to the sensors.

both. magnetic nanoparticles. Cancer will continue to be a big problem since it is a disease related mostly to age. Xavier Hailey. Developments in such areas as in nanoarrays.Nanotechnology in cancer prevention. 1996). improved nanoparticles (dendrimers. . introducing the authors to topics related to this report. In fact. Sang Jeong. many innovative and groundbreaking techniques have been developed in order to treat cancer (Diamandopoulus. cancer tended to be fatal in those who were unfortunate to develop it. There have been significant improvements largely due to breakthroughs. Throughout the bulk of human history. Michael Kent. critical reading of the manuscript and for providing us with useful corrective notes. Eugene Strashnov. Dave Higgs. Nanotechnology treatments can be used in both the preemptive and in the disease-time approaches to dealing with cancer. very recent breakthroughs in nanotechnology have managed to change all that. Tohru Yamada and Gucheng Zeng for their cooperation. diamondoids. An important aspect of cancer treatment is its early detection. monoclonal antibodies. Although there is still plenty of work to be done. in the bottom-up and in the top-down nanotechnology. Tapas Das Gupta. Maria Geno. Also other recent discoveries and inventions in nanotechnology are suggesting that a safe and effective cure for cancer is just around the corner. Now at last there is hope for a cure that is effective and can be made it safe. Acknowledgements The authors would like to thank Rob Barber. helpful comments. detection and treatment 251 8 Conclusion Prevention. and quantum dots) and nanoelectronics are making early detection. Over the past 150 years. we will gain the ability to treat various kinds of cancer more and more effectively. These techniques range from brute surgical removal to X-ray irradiation to system wide flooding with anticancer agents. Richard Magin. nanosensors. However. liposomes. Of course the hope is to turn cancer into a manageable ailment that we can treat and we can live with. As we become better able to engineer more sophisticated nanodevices and to equip them with effective targeting techniques for biomolecules. some very promising new nanotechnology treatment methods are in the works. As our population average age increases due to medical advances cancer will be a major disease of the aging. Kenneth Brandenburg. gold-based nanoparticles. On the contrary. prevention and treatment with a high degree of accuracy and ease possible. Achievement of this goal in the battle against cancer seems to be mostly due to the potential successes of dealing with cancer through nanotechnology. Dustin Swan. sufficient research funds and a determination to succeed. publications. cancer has long been considered an incurable disease and it is grouped with Hepatitis C and AIDS. diagnosis and treatment of cancer have always been a formidable medical challenge. Amir Nazem. The goal of the US National Cancer Institute is to eliminate the suffering and death from cancer by the year 2015. bibliography and write ups. each of these approaches has its own series of undesirable side effects that are both dangerous and damaging to the overall health of the patient.

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induces apoptosis. contains a copy of the DNA Endothelial cell. A thin. a molecule. A form of skin cancer that arises in melanocytes. de Broglie (Thermal) wavelength. removes dead cells due to apoptosis. and T is the absolute temperature. Name given to unprogrammed death of cells (compare with apoptosis – programmed cell death). Ali Mansoori et al. kB is the Boltzmann constant. A highly selective tumour marker expressed in some human cancers Glycoprotein = Oligosaccharide. or a molecular group that binds to another chemical entity to form a larger complex Macrophage. now called the de Broglie thermal wavelength.. In wave mechanics. where h is the Planck.e. In other words. except red blood cells. the de Broglie wavelength equation is λ = h/p = h/(mv) where p is the momentum. A type of white blood cell that surrounds and kills microorganisms. an ion. Cell death due to acute injury to cells like deprivation of blood supply Operon. The ability of a substance (i. a gene that codes for a protein that regulates the cell cycle. An operon contains one or more structural genes which are transcribed into RNA p53 = TP53. Λ = [h2/2πmkBT]1/2. flattened cell that lines the interior surface of blood vessels Fibroblast. A paracrine agent is an intercellular chemical messenger used for paracrine signalling. de Broglie postulated a connection between radiation of material particles and photons. spread of cancer cells from the original site to other parts of the body Monoclonal antibody. Peptide that inhibits tumour growth. In genetics it refers to the organic substances resulting from enzymatic reactions Metastasis. It is induced by exposure to significant sun exposure or high levels of UV radiation Metabolite. m is the mass and v is the velocity. A set of genes transcribed under the control of an operator gene and occurring in the cell nucleus. m is the particle’s rest mass. The carrier of genetic information. the type of antibody produced late in the immune response Immunogenicity. A tumour suppressor protein. A fluorophore commonly used in microscopy. An antibody that consists of a single type of immunoglobulin since it is produced artificially from a single cell clone Necrosis. prevents cell-cell adhesion and found on white blood cell and platelet surface Intermolecular relationships. A connective tissue cell found throughout the body FITC = Fluoresceine Iso Thio Cyanate. It is in the 53 kilodalton fraction of cell proteins Paracine signal.256 G. which passes from generation to generation. A radical. A small organic molecule. de Broglie discovered that all particles with momentum have a wavelength. A macromolecule composed of a protein and a carbohydrate congugate IgG = Immunoglobulin G = Immune Globulin G. releasing their contents and possibly damaging neighbouring cells provoking inflammation. the cells that produce the skin pigment. The form of signal by a living cell in which the target cell is close to the signal releasing cell. which is typically conjugated to proteins via primary amines Folate receptor. Forces and potentials due to attraction and repulsion between molecules Ligand. antigen. that wave-particle behaviour of radiation applies to matter. it expresses the momentum term in terms of thermal energy DNA = Deoxyribonucleic Acid. breaking open. Every cell in the body. vaccine) to stimulate an immune response Integrin-antagonist lipid. Cell death due to swelling. Examples are somatostatin and histamine . and stimulates the action of other immune system cells Melanoma. In 1924. Λ is the mean quantum mechanical wavelength of the molecules at temperature T.

derived from membranes either by a physiological process (budding) or mechanically by sonication. It is about identification of proteins in the body and the determination of their role in physiological and pathophysiological functions R-phycoerythrin. Unlike DNA. which correlates to poor prognosis Vesicle. Many tumours overexpress VEGF. A molecule similar to DNA which is found in the nucleus and cytoplasm of cells. A short compound formed by linking two or more amino acids. and neutrophils) that engulfs and digests debris and invading microorganisms Phagocytosis. The process whereby genetic information coded in messenger RNA directs the formation of a specific protein at a ribosome in the cytoplasm VEGF = Vascular Endothelial Growth Factor = Vascular permeability factor.Nanotechnology in cancer prevention. The process of messenger RNA syntheses from a DNA template resulting in genetic information transfer from DNA to RNA Transfection. The primary function of RNA is protein synthesis within a cell. There are several classes of RNA molecules TNF = Tumour Necrosis Factor Transcription (in genetics). Fluorescent proteins derived from cyanobacteria and eukaryotic algae. Vesicles of dimensions in excess of 50 nm are believed to be important in intracellular transport processes . The action of a phagocyte cell Proteomics. The introduction of foreign DNA into a cell Translation (in genetics). A protein made by oxygen-deprived cells (such as cancerous cells) that stimulates new blood vessel formation. monocytes. Their fluorescence is much higher than chemical fluorescent probes RNA = Ribonucleic acid. Proteins are made of multiple peptides 257 Phagocyte. RNA can leave the nucleus of the cell. detection and treatment Peptide. A cell (like macrophage. A closed membrane shell.

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