Quantum Dots and Carbon Nanotubes in Cancer diagnose EE453 Project Report submitted by Makram Abd El Qader

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1 Quantum Dots and Carbon Nanotubes in Cancer diagnose EE453 Project Report submitted by Makram Abd El Qader Fall 2008 Abstract On the basis of research and cancer medical treatment, technologists agree that it is clear that nanotechnology is ready today to solve significant problems in cancer research. certainly, one of the goals of the research institutes for Nanotechnology in Cancer is to increase the visibility and the ease of use of nanomaterials and nanoscale devices technology within the cancer research and development community to allow investigators the opportunity to do what they do best to find out and invent using new tools, just as they are doing with other disrupting technologies such as DNA microarrays and proteomic analysis. 1. Introduction Nanotechnology can have an early, paradigm-changing impact on how clinicians will detect cancer in its earliest stages. Delicately sensitive devices constructed of nanoscale components-such as nanocantilevers, nanowires, and nanochannels-offer the potential for detecting even the rarest molecular signals associated with malignancy. Collecting those signals for analysis could fall to nanoscale harvesters, already under expansion, that selectively isolate cancer-related molecules such as proteins and peptides present in minute amounts from the bloodstream or lymphatic system. Investigators have already demonstrated the feasibility of this approach using the serum protein albumin (a naturally existing Quantum Dots), which happens to collect proteins that can signal the presence of malignant ovarian tissue. 2. Quantum Dots in Cancer Detection 2.1 Quantum Dots Quantum dots, also known as nanocrystals, are a special class of materials known as semiconductors, which are crystals composed of periodic groups of II-VI, III-V, or IV-VI materials. A quantum dot is a particle of matter so small that the addition or removal of an electron changes its properties in some useful way. Semiconductor quantum dots as shown (in Fig.1) are nanoparticles that have attracted widespread interest in biology and medicine due to their unique optical and electronic properties. These properties, especially their reduced tendency to photobleach and the dependence of their fluorescence wavelength on their size, make them suitable for fluorescent probing applications to detect cancer biomarkers in cells and tissues. There is considerable interest among researchers due to the recent developments in Quantum Dots technology. Quantum Dots have been encapsulated in amphiphilic polymers and bound to tumour-targeting ligands and drug delivery vesicles for targeting, imaging and treating tumour cells.

2 Fig 1. Quantum Dots Structure 2.2 Quantum Dots in Early Diagnosis of Cancer Early screening of cancer is advantageous as most tumours are noticeable only when they reach a certain size when they contain millions of cells that may already have metastasized. Currently several methods are employed in cancer diagnostic such as medical imaging or tissue biopsy. Moreover, these assays are labour intensive, time consuming, expensive and don t have multiplexing capability. On the other hand, Quantum Dots based detection is rapid, easy and economical enabling quick point-of-care screening of cancer markers. Quantum Dots have got unique properties which make them ideal for detecting tumours. These include intense and stable fluorescence for a longer time; resistance to photobleaching [1-5], large molar extinction coefficients, and highly sensitive detection due to their ability to absorb and emit light very efficiently. Due to their large surface area-to-volume ratio, a single Quantum Dots can be conjugated to various molecules, thus making Quantum Dots appealing for employment in designing more complex multifunctional nanostructures. 2.3 Quantum Dots Target Mechanism Quantum Dots can be delivered to tumour cells by both active and passive targeting mechanisms although the passive targeting is much slower and less efficient than active targeting. In the passive targeting mechanism, Quantum Dots accumulate preferentially at tumour cells due to enhanced permeability and retention effect [6-8]. This effect can be attributed to the facts that angiogenic tumours first produce vascular endothelial growth factors, which are responsible for enhanced permeability, second lack an effective lymphatic drainage system, which results in Quantum Dots bioconjugates accumulation which could harm human body. On the other side in the active targeting mechanism, antibody-conjugated Quantum dots are employed where the antibody gets attached to their specific tumour biomarkers such as prostate specific membrane antigen present on the tumour cells at the target site.

3 2.4 Quantum Dots Research Many universities and agencies funded by the federal government and the NIH- National Institute of Health have successfully shown that quantum dots can be effectively used in diagnosing cancer. one of them is Carnegie Mellon University which has been able to take images of sentinel lymph nodes in animals using quantum dots and near infrared light as shown (in Fig2). Byron Ballou, PhD and his team have been able to map the lymph nodes that drain tumors in mouse models of human cancer. Their method was to inject quantum dots into the tumors they were then able to track the quantum dots through the skin by using near-infrared fluorescence microscopy. Byron s team was able to see the quantum dots move out of the tumors and into the lymph system. The team reported being able to see the quantum dots almost immediately after injection. [9] Fig. 2. Quantum Dot structure and its targeting mechanism on tumour cell 2.5 Quantum Dots negative side effects The safety of quantum dots in the usage to treat cancer is still being questioned by the FDA and other societies. Quantum dots are deplete many toxic due to the CdSe. However, different techniques of polymers and coatings have been used productively to keep toxicity from spreading away from the Dots. A group of researchers from NIH has been studying a group of

4 animals injected with quantum dots for couple of years, have successfully shown no side effects any ill affects on the animals that was caused by the quantum dots. 3. Carbon Nanotubes in Cancer Detection 3.1 Carbon Nanotubes Carbon nanotubes as shown (in Fig.3) have a unique nanostructure with remarkable electronic and mechanical properties. These cylindrical carbon molecules have a variety of properties that make them potentially useful in many applications in nanotechnology, electronics, optics and other fields of materials science. Their name is resulting from their size, since the diameter of a nanotube is in the order of a few nanometers approximately 1/50,000th of the width of a human hair, while they can be up to several millimeters in length [12]. Nanotubes are categorized as single-walled nanotubes (SWNTs) and multi-walled nanotubes (MWNTs). They are among the stiffest and strongest fibers known, for these reasons they have attracted huge academic and industrial interest, with thousands of papers on nanotubes being published every year. Fig 3. Nanotubes fabrication stage 3.2 Carbon Nanotubes in Early Diagnosis of Cancer Carbon nanotubes can function as bright Raman optical tags that are readily detected when irradiated with light. Experiments comparing the lower limits of protein detection using an antibody-labeled carbon nanotube tag and a standard fluorescence tag showed that the carbon nanotube-enabled assay was at least 1,000 times more sensitive than the fluorescence assay.

5 3. 2 Carbon Nanotubes Research Using an array of nanotube devices, each coated with a different organic material, researchers at the Israel Institute of Technology have developed diagnostic system that may be able to diagnose lung cancer simply by sampling a patient s breath. The results of this study, which was led by Hossam Haick, Ph.D., appear in the journal Nano Letters. Dr. Haick and his colleagues first created individual devices consisting of random networks of single-walled carbon nanotubes coated with 1 of 10 different insulating nonpolymeric organic materials[10]. The investigators used standard microprocessor fabrication techniques to create the sensors. Thanks to the different organic materials used to coat the nanotubes, each sensing device provided a unique response when exposed to wide variety of the more than 200 volatile organic chemicals present in human breath. 4. Conclusion Nanotechnology is the future of cancer treatment. Within the next few years it might be possible for this new technology to become the new standard for cancer detection. Quantum dots will allow doctors to properly track cancer and see how it develops within the human body. We need to invest in our own future and ensure that this promising new technology reaches its full potential.

6 References Chan W.C.W., Maxwell D.J., Gao X., Bailey R.E., Han M. and Nie S., Luminescent QDs for multiplexed biological detection and imaging, Curr. Opin. Biotechnol., 13, 40-46, Alivisatos A.P., Semiconductor clusters, nanocrystals, and quantum dots, Science, 271, , Han M., Gao X., Su J.Z. and Nie S., Quantum dot-tagged microbeads for multiplexed optical coding of biomolecules, Nat. Biotechnol., 19, , Niemeyer C.M., Nanoparticles, proteins, and nucleic acids: Biotechnology meets materials science, Angrew. Chem. Int. Ed. Engl., 40, , Leatherdale C.A., Woo W.K., Mikulec F.V. and Bawendi M.G., On the absorption cross section of CdSe nanocrystal quantum dots, J. Phys. Chem. B, 106, , Duncan R., The dawning era of polymer therapeutics, Nat. Rev. Drug Discov., 2, , Jain R.K., Transport of molecules, particles, and cells in solid tumors, Ann. Rev. Biomed. Eng., 1, , Jain R.K., Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function, J. Control. Release, 74, 7-25,