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NANOTUBES A NEWER APPROACH IN CANCER THERAPY: AN OVERVIEW

Interfacing carbon nanotubes with biological systems could lead to significant applications in various disease diagnoses. This article reviews the current trends in biological functionalization of carbon nanotubes and their potential applications for cancer diagnostics and treatment.

NANOTUBES A NEWER APPROACH IN CANCER THERAPY: AN OVERVIEW

Mishra, Lalit ^1*; Dwivedi, Sumeet²; Pandey, Deepak³; Dwivedi, Abhishek ⁴and Tomar, Singh, Gajendra¹   

1, Smriti College of Pharmaceutical Education, Indore, Madhya Pradesh, India

2, Chordia Institute of Pharmaceutical Education, Indore, Madhya Pradesh, India

3, Pentagon Labs, Dewas, Madhya Pradesh

4, NRI Institute of Pharmaceutical Science, Bhopal, Madhya Pradesh, India

ABSTRACT

A nanotube is a long cylinder whose diameter is just a few nanometers. Often, nanotubes are made of carbon. The carbon nanotube's structure can be thought of as a sheet of graphite which has been rolled into a cylinder. Nanotubes are defined not only by length and diameter, but also by chirality or "twist." A nanotube can also contain multiple cylinders of different diameters nested inside one another. This type is called a multi-wall nanotube (MWNT). A nanotube with just one cylinder is referred to as a single-wall nanotube (SWNT). Other varieties of nanotubes include ropes, bundles and arrays. The nanotube's structure is the key to determining its other properties, such as elasticity, mechanical strength, electrical conductance and thermal conductivity. Over the past two years, researchers have demonstrated repeatedly that certain types of carbon nanotubes are among the most effective materials known for transporting proteins, genes, and drug molecules across the cell membrane. Now, an attempt to better understand this process has found that virtually any type of carbon nanotube can enter a wide variety of cell types. Moreover, it appears carbon nanotubes enter cells using more than one mechanism. Nanotubes have many unique properties such as high surface area, hollow cavities, and excellent mechanical and electrical properties. Interfacing carbon nanotubes with biological systems could lead to significant applications in various disease diagnoses. Significant progress in interfacing carbon nanotubes with biological materials has been made in key areas such as aqueous solubility, chemical and biological functionalization for biocompatibility and specificity, and electronic sensing of proteins. In addition, the bioconjugated nanotubes combined with the sensitive nanotube-based electronic devices would enable sensitive biosensors toward medical diagnostics. Furthermore, recent findings of improved cell membrane permeability for carbon nanotubes would also expand medical applications to therapeutics using carbon nanotubes as carriers in gene delivery systems. This article reviews the current trends in biological functionalization of carbon nanotubes and their potential applications for cancer diagnostics. The present work complies the review on carbon nanotubes and its efficacy in treatment of cancer and also reports the mechanism and properties. 

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INTRODUCTION

Carbon nanotubes  (CNTs) are allotropes of carbon. A single-walled carbon nanotube (SWNT) is a one-atom thick sheet of graphite (called graphene) rolled up into a seamless cylinder with diameter of the order of a nanometer. This results in a nanostructure where the length-to-diameter ratio exceeds 10,000. Such cylindrical carbon molecules have novel properties that make them potentially useful in many applications in nanotechnology, electronics, optics and other fields of materials science. They exhibit extraordinary strength and unique electrical properties, and are efficient conductors of heat. Inorganic nanotubes have also been synthesized. Nanotubes are members of the fullerene structural family, which also includes buckyballs. Whereas buckyballs are spherical in shape, a nanotube is cylindrical, with at least one end typically capped with a hemisphere of the buckyball structure. Their name is derived from their size, since the diameter of a nanotube is in the order of a few nanometers (approximately 50,000 times smaller than the width of a human hair), while they can be up to several millimeters in length. There are two main types of nanotubes: single-walled nanotubes (SWNTs) and multi-walled nanotubes (MWNTs).

The nature of the bonding of a nanotube is described by applied quantum chemistry, specifically, orbital hybridization. The chemical bonding of nanotubes are composed entirely of sp² bonds, similar to those of graphite. This bonding structure, which is stronger than the sp³ bonds found in diamond, provides the molecules with their unique strength. Nanotubes naturally align themselves into "ropes" held together by Van der Waals forces. Under high pressure, nanotubes can merge together, trading some sp² bonds for sp³ bonds, giving great possibility for producing strong, unlimited-length wires through high-pressure nanotube linking.

TYPES OF CARBON NANOTUBES

1.      Single-walled

2.       Multi-walled

3.       Fullerite

4.       Torus

5.       Nanobud

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Single-walled nanotubes (SWNT)

It have a diameter of close to 1 nanometer, with a tube length that can be many thousands of times longer. The structure of a SWNT can be conceptualized by wrapping a one-atom-thick layer of graphite called graphene into a seamless cylinder. The way the graphene sheet is wrapped is represented by a pair of indices (n,m) called the chiral vector. The integers n and m denote the number of unit vectors along two directions in the honeycomb crystal lattice of graphene. If m=0, the nanotubes are called "zigzag". If n=m, the nanotubes are called "armchair". Otherwise, they are called "chiral".

Single-walled nanotubes are a very important variety of carbon nanotube because they exhibit important electric properties that are not shared by the multi-walled carbon nanotube (MWNT) variants. Single-walled nanotubes are the most likely candidate for miniaturizing electronics beyond the micro electromechanical scale that is currently the basis of modern electronics. The most basic building block of these systems is the electric wire, and SWNTs can be excellent conductors. One useful application of SWNTs is in the development of the first intramolecular field effect transistors (FETs). The production of the first intramolecular logic gate using SWNT FETs has recently become possible as well. To create a logic gate you must have both a p-FET and an n-FET. Because SWNTs are p-FETs when exposed to oxygen and n-FETs when unexposed to oxygen, they were able to protect half of a SWNT from oxygen exposure, while exposing the other half to oxygen. The result was a single SWNT that acted as a NOT logic gate with both p and n-type FETs within the same molecule.

Multi-walled

Multi-walled nanotubes (MWNT) consist of multiple layers of graphite rolled in on themselves to form a tube shape. There are two models which can be used to describe the structures of multi-walled nanotubes. In the Russian Doll model, sheets of graphite are arranged in concentric cylinders, e.g. a (0,8) single-walled nanotube (SWNT) within a larger (0,10) single-walled nanotube. In the Parchment model, a single sheet of graphite is rolled in around itself, resembling a scroll of parchment or a rolled up newspaper. The interlayer distance in multi-walled nanotubes is close to the distance between graphene layers in graphite, approximately 3.3 Å. The special place of double-walled Carbon Nanotubes (DWNT) must be emphasized here because they combine very similar morphology and properties as compared to SWNT, while improving significantly their resistance to chemicals. This is especially important when functionalisation is required (this means grafting of chemical functions at the surface of the nanotubes) to add new properties to the CNT. In the case of SWNT, covalent functionalisation will break some C=C double bonds, leaving "holes" in the structure on the nanotube and thus modifying both its mechanical and electrical properties. In the case of DWNT, only the outer wall is modified. DWNT synthesis on the gram-scale was first proposed in 2003 by the CCVD technique, from the selective reduction of oxides solid solutions in methane and hydrogen.

Fullerite

Fullerites are the solid-state manifestation of fullerenes and related compounds and materials. Being highly incompressible nanotube forms, polymerized single-walled nanotubes (P-SWNT) are a class of fullerites and are comparable to diamond in terms of hardness. However, due to the way that nanotubes intertwine, P-SWNTs don't have the corresponding crystal lattice that makes it possible to cut diamonds neatly. This same structure results in a less brittle material, as any impact that the structure sustains is spread out throughout the material.

Torus

A nanotorus is a theoretically described carbon nanotube bent into a torus (donut shape). Nanotori have many unique properties, such as magnetic moments 1000 times larger than previously expected for certain specific radii. Properties such as magnetic moment, thermal stability, etc. vary wdely depending on radius of the torus and radius of the tube.

Nanobud

Carbon NanoBuds are a newly discovered material combining two previously discovered allotropes of carbon: carbon nanotubes and fullerenes. In this new material fullerene-like "buds" are covalently bonded to the outer sidewalls of the underlying carbon nanotube. This hybrid material has useful properties of both fullerenes and carbon nanotubes. In particular, they have been found to be exceptionally good field emitters. 

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CNT MOLECULAR MODELING SOFTWARE

·         CoNTub v1.0

·        Nanorex

·         Wrapping

·         Nanotube Modeller

·         TubeASP

·         Tubegen

·         Materials Studio 4.2

1-CoNTub- CoNTub is software written in Java which runs on Windows, Mac OS X, Linux and Unix Operating systems. It is the first implementation of an algorithm for generating the 3D structure of two arbitrary connected carbon nanotubes by means of one defect or disclination (pentagonal or heptagonal).

The software is a set of tools dedicated to the construction of complex carbon nanotube structures for use in computational chemistry. CoNTub¹ is the first implementation of building these complex structures, including nanotube heterojunctions, for designing and investigating new nanotube-based devices. CoNTub is based on strip algebra, and is able to find the unique structure for connecting two specific and arbitrary carbon nanotubes.

CoNTub allows the geometry of some two-tube heterojunctions to be easily generated, including single-walled nanotubes (SWNTs) and multi-walled nanotubes (MWNTs). The program itself is organized in five Tabbed panelsCoNTub, the first three being dedicated to structure generation, the fourth to the output in PDB format, and the fifth contains a short help section.{mospagebreak}

FUTURE PROSPECTS

 Application of Nanotechnology in Electronic Devices

Nanomaterials are produced by two methods, the bottom up and top down. The bottom up method has been successfully used for self assembly by researchers through out the world. The bottom up method especially is therefore useful for ionic and electronic applications, however top down method plays a major role in research in many US universities and companies.

One of the important applications of nanotechnology is in advance architecture level of the Si-LSI technology. One method of constructing an electronic device is using bottom up method and combining it with top down method.

Many researchers has used bottom up method to fabricate a DRAM capacitor. DRAM comprises a pair of transistor and capacitor. Scientists at University of California have successfully fabricated a two-layered dielectric film. The dielectric film contains a self assembled monolayer and electrolyte. The redox reduction between SAM and electrolyte controls the capacitance and electromotive force within the dielectric film.

Flash memeory is another important application of nanotechnology. In conventional flash memory, a unit of single transistor is used. Highly integrated flash memory, a major non-volatile memory is in high demand for portable devices such as mobile phones. A floating gate stores the charge in the flash memory and these floating gates are being replaced by number of nanodots. These nanodots are non-continuous film and work smoothly even when the film contains certain amount of defects. So, the flash memory is far better than the conventional semiconductor memory.

 Nanomedicine: current status and future prospects

Applications of nanotechnology for treatment, diagnosis, monitoring, and control of biological systems has recently been referred to as "nanomedicine" by the National Institutes of Health. Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine. These involve the identification of precise targets (cells and receptors) related to specific clinical conditions and choice of the appropriate nanocarriers to achieve the required responses while minimizing the side effects. Mononuclear phagocytes, dendritic cells, endothelial cells, and cancers (tumor cells, as well as tumor neovasculature) are key targets. Today, nanotechnology and nanoscience approaches to particle design and formulation are beginning to expand the market for many drugs and are forming the basis for a highly profitable niche within the industry, but some predicted benefits are hyped. This article will highlight rational approaches in design and surface engineering of nanoscale vehicles and entities for site-specific drug delivery and medical imaging after parenteral administration.{mospagebreak}

NANOSIZED TECHNOLOGIES FOR MEDICAL IMAGING AND TARGETED DRUG DELIVERY

·         Nanoparticles with inherent diagnostic properties

Nanotechnology is an area of science devoted to the manipulation of atoms and molecules leading to the construction of structures in the nanometer scale size range (often 100 nm or smaller), which retain unique properties. Indeed, the physical and chemical properties of materials can significantly improve or radically change as their size is scaled down to small clusters of atoms. Small size means different arrangement and spacing for surface atoms, and these dominate the object’s physics and chemistry Colloidal gold, ironoxide crystals, and quantum dots (QDs) semiconductor nanocrystals are examples of nanoparticles, whose size is generally in the region of 1–20 nm, and have diagnostic applications in biology and medicine . Gold nanoparticles have application as quenchers in fluorescence resonance energy transfer measurement studies. For example, the distance-dependent optical property of gold nanoparticles has provided opportunities for evaluation of the binding of DNA-conjugated gold nanoparticles to a complementary RNA sequence Iron oxide nanocrystals with superparamagnetic properties are used as contrast agents in magnetic resonance imaging (MRI), as they cause changes in the spin-spin relaxation times of neighboring water molecules, to monitor gene expression or detect pathologies such as cancer, brain inflammation, arthritis, or atherosclerotic plaques. QDs can label biological systems for detection by optical or electrical means in vitro and to some extent in vivo The fluorescence emission wavelength (from the UV to the near-IR) of QDs can be tuned by altering the particle size, thus these nanosystems have the potential to revolutionize cell, receptor, antigen, and enzyme imaging. Indeed, a recent report demonstrated the use of QDs for tracking metastatic tumor cell extravasation (20) Their large surface area-to-volume ratio offers potential for designing multifunctional nanosystems.Undoubtedly, application of such multi-wavelength optical nanotools may eventually aid our understanding of the complex regulatory and signaling networks that govern the behavior of cells in normal and disease states.

·         Nanovehicles and drug carriers

In addition, there are numerous engineered constructs, assemblies, architectures, and particulate systems, whose unifying feature is the nanometer scale size range (from a few to 250 nm). These include polymeric micelles, dendrimers, polymeric and ceramic nanoparticles, protein cage architectures, viral-derived capsid nanoparticles, polyplexes, and liposomes . First, therapeutic and diagnostic agents can be encapsulated, covalently attached, or adsorbed on to such nanocarriers. These approaches can easily overcome drug solubility issues, particularly with the view that large proportions of new drug candidates emerging from high-throughput drug screening initiatives are water insoluble. But some carriers have a poor capacity to incorporate active compounds (e.g., dendrimers, whose size is in the order of 5–10 nm). There are alternative nanoscale approaches for solubilization of water insoluble drugs. One approach is to mill the substance and then stabilize smaller particles with a coating; this forms nanocrystals in size ranges suitable for oral delivery, as well as for intravenous injection. Thus, the reduced particle size entails high surface area and hence a strategy for faster drug release. Pharmacokinetic profiles of injectable nanocrystals may vary from rapidly soluble in the blood to slowly dissolving. Second, by virtue of their small size and by functionalizing their surface with synthetic polymers and appropriate ligands, nanoparticulate carriers can be targeted to specific cells and locations within the body after intravenous and subcutaneous routes of injection. Such approaches, may enhance detection sensitivity in medical imaging, improve therapeutic effectiveness, and decrease side effects. Some of the carriers can be engineered in such a way that they can be activated by changes in the environmental pH, chemical stimuli, by the application of a rapidly oscillating magnetic field, or by application of an external heat source^. Such modifications offer control over particle integrity, drug delivery rates, and the location of drug release, for example within specific organelles. Some are being designed with the focus on multifunctionality; these carriers target cell receptors and delivers simultaneously drugs and biological sensors. Some include the incorporation of one or more nanosystems within other carriers, as in micellar encapsulation of QDs; this delineates the inherent nonspecific adsorption and aggregation of QDs in biological environments In addition to these, nanoscale-based delivery strategies are beginning to make a significant impact on global pharmaceutical planning and marketing (market intelligence and life-cycle management)

·         Carbon Nanotube Membrane for controlled transportation

Various researchers have already studied fluid flow in micrometer level carbon nanotube channels. These open-ended carbon nanotube offer various possibilities as conduits for flow especially for low surface tension fluid as these nanomaterials have excellent rigid cylindrical pores. Selected microfabrication technique can enhance the possibilities for development of various small-scale-devices. These small-scale devices or lab-on-a-chip can play a key role in chemical analysis or synthesis.

Actually modifying their surfaces, scientists can enhance the molecular selectivity of carbon nanotubes. Researchers has already established various applications of nanotubes or nanopores such as molecule detection, storage and delivery of encapsulation media, biocatalysis, biomolecule separation devices and for selective and rapidgas flow. Researchers have studied and fabricated a well-ordered membrane structure by aligning array of carbon nanotubes impregnated in polystyrene matrix.

The open tips of carbon nanotube in the membrane structure are attached with carboxylate that can be easily functionalized. This functionalization especially with a bulky receptor can subsequently be used to open or close the pore. Thus the membrane structure is suitable for the gas flow or ionic transport. Recently researchers have fabricated functionalized carbon nanotube at the end and its application as ionic transport has been achieved. Researchers could achieve this by releasing receptor in controlled fashion.

Scientists have also developed an inner-coated carbon nanotube. Here the inside walls of carbon nanotubes within the carbon nanotube membrane contains the redox-active polymer film. The specifically selected polymer film can be reversibly switched electrochemically and therefore it controls both the directionand magnitude of electroosmotic flow through carbon nanotube membrane.{mospagebreak}

OTHER PROSPECT

• Future prospects for nanotube applications in high integrated circuits
• Nanowires
• Bionanodevices in Bionanotechnology
• Nanotechnology and Neural Interfaces
• Morphological varieties of Carbon Nanotubes
• Nanodevices from conducting polymers
• Passivated Nanoparticles
• Structural, Electronic and optical properties of Semiconductor Nanocrystals
• Carbon Nanotube Membrane for controlled transportation
• Research on Gold Nanoparticles

CONCLUSION

Carbon nanotubes have remarkable electronic and mechanical properties and have been shown to exhibit very interesting mesoscopic phenomena. We study electronic transport across individual single-wall carbon nanotubes

Carbon nanotubes are molecular-scale tubes of graphitic carbon with outstanding properties. They are among the stiffest and strongest fibres known, and have remarkable electronic properties and many other unique characteristics. For these reasons they have attracted huge academic and industrial interest, with thousands of papers on nanotubes being published every year. Commercial applications have been rather slow to develop, however, primarily because of the high production costs of the best quality nanotubes.

Big markets, apart from materials, in which nanotubes may make an impact, include flat panel displays (near-term commercialization is promised here), lighting, fuel cells and electronics. This last is one of the most talked-about areas but one of the farthest from commercialization, with one exception, this being the promise of huge computer memories (more than a thousand times greater in capacity than what you probably have in your machine now) that could, in theory, put a lot of the $40 billion magnetic disk industry out of business. Companies like to make grand claims, however, and in this area there is not just the technological hurdle to face but the even more daunting economic one, a challenge made harder by a host of competing technologies.

Despite an inevitable element of hype, the versatility of nanotubes does suggest that they might one day rank as one of the most important materials ever discovered. In years to come they could find their way into myriad materials and devices around us and quite probably make some of the leaders in this game quite rich.

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