Saturday, April 4, 2015

APPLICATION OF NANOTECHNOLOGY - NANOMEDICINES

Nanotechnology in Medicine:
The Medicine of Tomorrow and Nanomedicine

Logothetidis S

Aristotle University of Thessaloniki, Physics Department
Lab for Thin Films - Nanosystems & Nanometrology, GR-54124 Thessaloniki, Greece

Abstract

Nanotechnology is an emerging technology with enormous potential in information and communication technology, biology and biotechnology, medicine and medical technology. Novel nano- and bio-materials, and nanodevices are fabricated and controlled by nanotechnology tools and techniques, which investigate and tune the properties, responses and functions of living and non-living matter, at sizes below 100 nm. The current advances of nanotechnology in modern medicine are presented and discussed. The potential medical applications are predominantly in detection, diagnostics (disease diagnosis and imaging), monitoring, and therapeutics. The availability of more durable and better prosthetics, and new drug-delivery systems are of great scientific interest and give hope for cancer treatment and minimum invasive treatments for heart disease, diabetes and other diseases. Many novel nanoparticles and nanodevices are expected to be used, with an enormous positive impact on human health. The vision is to improve health by enhancing the efficacy and safety of nanosystems and nanodevices. Products based on nanotechnology in medicine and medical technology are reaching the market, with an anticipated enormous positive impact on human health, in the coming years. The development of specific guidance documents at a European level for the safety evaluation of nanotechnology products in medicine is strongly recommended and the need for further research in nanotoxicology, is identified. Ethical and moral concerns also need to be addressed in parallel with the new development.

1.     Introduction


 Nanoscale is generally considered to be at a size below 0.1 µm or 100 nm (a nanometer is one billionth of a metre, 10-9 m) (Figure 1). Nanoscale science (or nanoscience) studies the phenomena, properties and responses of materials at atomic, molecular and macromolecular scales, and in general at sizes between 1-100 nm. In this scale, and especially below 5 nm, the properties of matter differ significantly (i.e. quantum scale effects play an important role) from that at a larger particulate scale. Nanotechnology is then the design, the manipulation, the building, the production and application, by controlling the shape and size, the propertiesresponses and functionality of structures, devices and systems of the order or less than 100 nm. Figure 1 shows objects and living units whose size is or occur basically in the nanoscale, are also shown higher order structures of biological units or organisms at micro- meso- and macroscale, made by nature the last 4 billion years due to the ability to self- assemble and selforganize. In the same figure (on the right) are shown those objects man made at nano- and microscale during the last few years. Nowadays, scientists and technologists are learning from nature, and by applying the laws of physics, the properties of chemistry and the principles of biology, they create the era of nanotechnology. Nanotechnology is considered an emerging technology due to the possibility to advance well established products and to create new products with totally new characteristics and functions with enormous potential in a wide range of applications. In addition to various industrial uses, great innovations are foreseen in information and communication technology, biology and biotechnology, medicine and medical technology, in metrology, etc. It is anticipated that nanotechnology can have an enormous positive impact on human health. Relevant processes of living organisms occur basically at nanometer scale, elementary biological units like DNA, proteins or cell membranes are of this dimension (Figure 1). By the means of nanotechnology, these biological units are going to be better comprehended so that they can be specifically guided or directed. Miniaturisation down to nanometer scale provides to become an essential feature of biomedical products and procedures in postgenomic era. Nanoscale devices could be 100 to 10,000 times smaller than human cells but are similar in size to large biomolecules such as enzymes and receptors. Nanoscale devices smaller than 50 nm can easily enter most cells, and those smaller than 20 nm can move out of blood vessels as they circulate through the body.
    Huge aspirations are coupled to nanotechnological developments in modern medicine (Nanotechnology, Biotechnology, Information Technology & Cognitive Science - NBIC developments). The potential medical applications are predominantly in diagnostics (disease diagnosis and imaging), monitoring, the availability of more durable and better prosthetics, and new drug-delivery systems for potentially harmful drugs1 , as shown in Figure 2. For example, nanoscaled diagnostics are expected to identify in the becoming, giving the opportunity to intervene specifically prior to a symptomatically detected onset disease. Biomedical nanotechnology presents revolutionary opportunities in the fight against many diseases. An area with near-term potential is detecting molecules associated with diseases such as cancer, diabetes mellitus, neurodegenerative diseases, as well as detecting microorganisms and viruses associated with infections, such as pathogenic bacteria, fungi, and HIV viruses. For example, in the field of cancer therapy, promising novel nanoparticles will respond to externally applied physical stimuli in ways that make them suitable therapeutics or therapeutic delivery systems. Another important field of application for nanotechnology are biomaterials used for example in orthopedic implants or as scaffolds for tissue engineered products. Nanotechnology might yield nano-structured surfaces preventing non-specific protein adsorption. Control of surface properties at nanolevel was shown to increase the biocompatibility of the materials.

2.      Nanomaterials and nanoparticles in medicine: A new concept


Novel nanomaterials and nanoparticles are envisaged to have a major impact on a number of different relevant areas. Materials with high performance and unique properties can be produced, that traditional synthesis and manufacturing methods could not create.
Future nanoparticles should act as drug-delivery and drug- targeting systems. Due to their smallness they are not recognized by the human body, migrate through cell membranes beneath a critical size and are able to pass the blood - brain barrier. These characteristics are used to develop nanoscaled ferries, which transport high potential pharmaceutics precisely to their destination. There are different kinds of nanoparticles which are suitable to be applicable in drug- and gene- delivery, probing DNA structures, etc, and are categorized as: liposomes, polymer nanoparticles (nanospheres and nanocapsules), solid lipid nanoparticles, nanocrystals, polymer therapeutics such as dendrimers, fullerenes (most common as C60 or buckyball, similar in size of hormones and peptide a-helices), inorganic nanoparticles (e.g. gold and magnetic nanoparticles). Carbon nanotubes (diameter of 1-20 nm, as shown in Figure 3a) and inorganic nanowires exhibit extraordinary mechanical, electric, electronic, thermal, and optical properties offering the electronic industry properties that few materials platforms could ever hope to match. Carbon nanotubes, and magnetic iron oxide nanoparticles, gold-coated silica nanoshells, can transform electro-magnetic energy into heat, causing a temperature increase lethal to cancer cells merely by increasing the magnetic field or by irradiation with an external laser source of near infra red light at the very location where these nanoparticles are bound to or internalised within tumour cells2 . Quantum dots (nanometer sized semiconductor nanocrystals with superior fluorescent properties, as shown in Figure 3b) possess remarkable optical and electronic properties that can be precisely tuned by changing their size and composition, due to their very small size (2-10 nm). Due to their relatively inexpensive and simple synthesis, quantum dots have already entered the market for experimental biomedical imaging applications. Quantum dots can be made to emit light at any wavelength in the visible and infrared ranges, and can be inserted almost anywhere, including liquid solution, dyes etc. Quantum dots can be attached to a variety of surface ligands, and inserted into a variety of organisms for in-vivo research.
Dendrimers (complex almost spherical macromolecules with diameter 1-10 nm, shown in Fig.3c) have improved physical, chemical, and biological properties compared to traditional polymers. Some unique properties are related to their globular shape and the presence of internal cavities offering the possibility as medical nanovehicles. Dendrimers have a tree-like structure with many branches where a variety of molecules, including drugs can be attached. Less than 5 nm in diameter, dendrimers are small enough to slip through tiny openings in cell membranes and to pass vascular pores and tissues in a more efficient way than bigger polymer particles. In experiments reported in Cancer Research, University of Michigan scientists attached methotrexate, a powerful anticancer drug, to branches of the dendrimer (Figure 3c). On other branches, they attached fluorescent imaging agents and a vitamin called folic acid2,3. In addition to these examples of individual nanoparticles, novel biomaterials can be constructed using structural surface modifications of macro-, microas well as nanomaterials. Control of surface properties at nanolevel was shown to increase the biocompatibility of the materials2 . Nanoparticles, as shown in Figure 4, being the fundamental elements of nanotechnology, can be applied in various ways such as fluorescent biological markers, as markers for detection of proteins, probing of DNA structures and for separation and purification of biological molecules and cells, and they can also be used for magnetic resonance imaging enhancement, tumour destruction via heating, tissue engineering and drug, gene delivery. As an example, two kinds of nanoparticles that are suitable to be applicable at least in drug-delivery will be described: First, gold nanoparticles (3-20 nm), that are gold composites with dielectrical cores and golden shells. By choosing the right ratio of core to shell diameters the particle can be tuned to absorb highly in the near infrared, and by irradiation with such wavelength can be heated, even in deeper skin areas. If the particles are embedded in a temperature sensible hydrogenlmatrix, the matrix will collapse and the included agents will be released at a critical temperature.

  For applications to medicine and physiology, these nanomaterials, nanoparticles and devices can be designed to interact with cells and tissues at a molecular (i.e., subcellular) level with a high degree of functional specificity, thus allowing a degree of integration between technology and biological systems not previously attainable. It should be appreciated that nanotechnology is not in itself a single emerging scientific discipline but rather a meeting of traditional sciences such as chemistry, physics, materials science, and biology to bring together the required collective expertise needed to develop these novel technologies4 . On the other hand, due to advances in biochemical research and molecular biology diseases can put down to molecular abnormalities. Molecular imaging should detect the corresponding molecular signatures of diseases and use it for medical diagnosis. This should ideally lead to a diagnose and therapy before occurrence of symptoms. In molecular imaging, an imaging molecule is coupled to a transport molecule or particle, which possesses a targeting unit (e.g. special receptors, ligands or peptides). The target finding system should be a specific molecular marker of a certain disease thus the contrast medium accumulates within the sick tissue. Molecular imaging is developed for several diagnostic procedures such as magnetic resonance, ultrasonic imaging, as well as nuclear and optical imaging technologies.

3.      Nanotechnology Tools in Medicine.


Different methods for the synthesis of nanoengineered materials and devices can accommodate precursors from solid, liquid or gas phases and encompass a tremendously varied set of experimental techniques. A detailed presentation of these are beyond the scope of this review. In general, however, most synthetic methods can be classified into two main approaches: “top-down” and “bottom-up” approaches and combinations of them. “Top-down” (photolithography, microcontact printing) techniques begin with a macroscopic material or group of materials and incorporate smaller-scale details into them, whereas “bottom-up” (organic-synthesis, self-assembly) approaches, begin by designing and synthesizing custom-made molecules that have the ability to self-assemble or self-organize into higher order mesoscale and macroscale structures4 . There are several nanotechnology-based synthesis techniques of these materials. For example, carbon nanotubes, are developed by electric arc discharge, laser ablation, and chemical vapour deposition techniques. Various inorganic nanotubes are developed by arc discharge, and laser ablation, as well as through appropriate chemical reactions. Nanowire properties can differ distinctly from those of their corresponding crystalline bulk materials, though, some properties are similar. Nanowires can be synthesized using a large variety of materials such as metals, e.g. Ag, semimetals, e.g. Bi, semiconductors, e.g. CdS, and superconductors. The most common synthesis methods are template-assisted synthesis, including vapour and electrochemical deposition, and vapour-liquid-solid growth, especially successful for semiconductor nanowires. Dendrimers were first synthesized by an iterative synthetic methodology. The iterative sequence of reaction steps leads to a higher generation dendrimer after each iteration. The creation of dendrimers, using specifically-designed chemical reactions, is one the best examples of controlled hierarchical synthesis, an approach that allows the “bottom-up” creation of complex systems. The functional end groups can be modified for various purposes, including sensing, catalysis or biochemical activity. Other advanced applications of micro- and nanotechnology in medicine are the microchip-based drug delivery systems, which are devices incorporating micrometer-scale pumps, valves and flow channels. They allow controlled release of single or multiple drugs on demand. Micro- and nanotechnology-based methods (e.g., UV-photolithography, reactive ion etching, chemical vapour deposition, electron beam evaporation) can be used for the fabrication of these silicon-based chips. A myriad of studies is available for applications of micro- and nanotechnologies in chips for medical molecular diagnostics. Key words are for example DNA microarrays (gene chips), protein microarrays (protein chips), lab-on-a-chip devices (Figure 5a), and cell chips. Basically, these devices or systems are constructed using techniques inspired from micro/nanoscale fabrication methods, that are used for processing, manipulation, delivery, analysis or construction of biological and chemical entities. Inkjet printing methods are used in DNA microarrays for human genomics and in protein microarrays (or protein chips), which are useful for molecular diagnostics. For the subsequent readout detection either fluorescence- or radionuclide-based markers, or surface plasmon resonance spectroscopy can be applied.

   In order to study and explore these rich and complex systems, highly sophisticated experimental, theoretical and modelling tools are required. Especially, the visualization, characterization, and manipulation of materials and devices require sophisticated imaging and quantitative techniques with spatial and temporal resolutions on the order of 10-6 (a micron — a red cell is 7 microns) and below to the molecular level. In addition, these techniques are critical for understanding the relationship and interface between nanoscopic and mesoscopic/macroscopic scales, a particularly important objective for biological and medical applications. As such, further nanotechnological advances will necessitate parallel progress of these physical characterization techniques. Examples of important tools available at the moment include: highly focused (i.e., 1–2 ìm) synchrotron X-ray sources and related techniques that provide detailed molecular structural information by directly probing the atomic arrangement of atoms (Figure 5b); scanning probe microscopy (STM, AFM) that allow three dimensional-type topographical atomic and molecular views or optical responses (SNOM) of nanoscale structures (Figure 5c); in situ monitoring techniques that allow the monitoring and evaluation of building block assembly and growth13; ellipsometry, an optical method, with the capability of measuring in liquid environment (e.g, protein solution) to study protein and cells adsorption on solid surfaces6 , it has been employed to discriminate and identify bacteria at the species level, and is very promising for analytical purposes in biochemistry and in medicine.

4.       Medical Applications of Nanotechnology and Nanomedicine




Nanotechnology offers important new tools with a great impact on many areas in medical technology. It provides extraordinary opportunities not only to improve materials and medical devices but also to create new “smart” devices and technologies where existing and more conventional technologies may be reaching their limits. In the following these definitions related with new research areas and terms (i.e. nanobiotechnology, nanomedicine, nanodevices, “nanorobots”) will be given and then some of myriad applications of nanotechnology in modern medicine will be discussed in more detail
Nanomedicine: The convergence of recent advances in nanotechnology with modern biology and medicine has created the new research domain of nanobiotechnology. The use of nanobiotechnology in medicine is termed nanomedicine. Thus, nanomedicinean offshoot of Nanotechnology, referring to highly specific medical intervention at the molecular scale for therapeutic purposes (involving curing diseases or repairing damaged tissues), and for the development of diagnostics for rapid monitoring, targeted cancer therapies, localized drug delivery, improved cell material interactions, scaffolds for tissue engineering, and gene delivery systems. Successful research and development in nanomedicine where ultimately patients can benefit from these new technologies require the interaction of a multitude of disciplines including material science and engineering, cellular biology and clinical translational research.
      Many scientific as well as economic activities are expected to accelerate medical research and development. Several medical devices2 have already benefited from recent developments in micro- nanotechnology (see Table 1) and are in use or are currently being commercialized (Figures 5 and 7). Nanomaterials and biological structures are approximately of the same size, which allows for unique interactions between biological systems and synthetic materials for analytical, diagnostic and therapeutic applications.
nisms in living cells. “Nanorobots” and nanodevices: Such future devices are, for example, the artificial mechanical red blood cell or “respirocyte” (spherical shape of 1ìm diameter) and an artificial mechanical white blood cell of microscopic size, called a “microbivore” (3.4 ìm major axis diameter and 2.0ìm minor axis diameter). The “respirocyte” is expected to be able to deliver more oxygen to the tissues than natural red blood cells and to manage carbonic acidity. Primary medical applications of respirocytes would include transfusable blood substitution; partial treatment for anemia, lung disorders, enhancement of cardiovascular/neurovascular procedures, tumour therapies and diagnostics, prevention of asphyxia, artificial breathing, and a variety of sports, veterinary and battlefield. The primary function of “microbivore” is to destroy microbiologic pathogenat the cellular level, performing in-vivo cytosurgery. The most likely site of pathologic function in the cell is the nucleus – more specifically, the chromosomes. In one simple cytosurgical procedure called “chromosome replacement therapy”, a “nanorobot” controlled by a physician would extract existing chromosomes from a particular diseased cell and insert new ones in their place, in that same cell. If the patient chooses, inherited defective genes could be replaced with non defective base-pair sequences, permanently curing a genetic disease. Engineered bacterial “biobots” (synthetic microbes) may be designed to produce useful vitamins, hormones, enzymes or cytokines in which a patient’s body was deficient or to selectively absorb and metabolize harmful substances such as poisons, toxins etc into harmless end products.
   Biocompatibility and Orthopedic implants: An important field of application for nanotechnology in medicine is the biomaterials, used for example in orthopedic implants or as scaffolds for tissue engineered products. If the design of a hip implant, for instance (Figure 2), is carried out at nanolevel, it might become possible to construct an implant which closely mimics the mechanical properties of human bone, preventing stress-shielding and the subsequent loss of surrounding bone tissue2 . Extra-cellular matrix (ECM) provides an excellent three-dimensional web of intricate nanofibers to support cells and present an instructive background to guide their behaviour. It takes a variety of forms in different tissues and at different stages of development in the same tissue. This diversity arises through combinations of specific molecular interactions and geometrical arrangements of collagens, elastins, proteoglycans, and adhesion proteins, such as fibronectins and laminins. Unwnding the fibers of ECM, reveals a level of detail unmatched outside the biological world. Each fiber hides clues that pave the way for cells to form tissues, as complex as bone, liver, heart and kidney. A key challenge is to capture the degree of complexity that is needed to functionally replicate the ECM of natural tissue. Nevertheless, we are still a long way from recreating the molecular architecture of the ECM and the dynamic mechanisms by which information is revealed in response to challenges within the local environment. Nanostructuring of materials provides a powerful mechanism to encourage and direct cell behaviour, ranging from cell adhesion to gene expression, thus enhancing their biocompatibility, by dictating the desirable interactions between cells and materials. The question of how cells detect and respond to nanofeatures is unresolved yet. However, there are early findings, where the promotion of one cell type over another, such as osteoblasts (bone-forming cells) over osteoclasts (bone-resorbing cells), to stimulate bone growth, will be important in reducing aseptic loosening and failure of implants. It has been found that not only the scale of topography (5 nm to micrometer scale) modulates cell behaviour, but also the type of ordered topography (e.g., ridges, steps, grooves, pillars, and pits) and even their symmetry (e.g., orthogonal or hexagonal packing of nanopits) 32. Furthermore, surface modifications at nanolevel of biomaterials or their coatings might greatly enhance the biocompatibility by favouring the interaction of living cells with the biomaterial, especially by their beneficial effect on cell adhesion and proliferation. Together with the control of nanoporosity allowing vascularisation and the growth of cells inside the biomaterial, the nano-structured surfaces of biomaterials also allow the creation of novel types of scaffolds for tissueengineered products2 . Nanotechnology in Cardiology: Nanotechnology has various applications in the field of cardiology research not only for diagnostic but also for therapeutical purposes14. On the therapeutical scope, minimally invasive treatments for heart disease, diabetes and other diseases is a desirable goal for scientists, and there is hope for it, because of the use of nanotechnology. More precisely, a team led by Paul Grayburn of Baylor University Medical Center, and Ralph Shohet of the University of Texas Southwestern Medical School, in Dallas, Texas, has demonstrated that ultrasound-targeted microbubble destruction (Figure 8) can deliver genes that stimulate the growth of new blood vessels in rat heart.
       Cardiovascular gene therapy could be realized roughly as follows: identification of a protein whose presence causes blood vessels to form, production and packaging of strands of DNA that contain the gene for making the protein and deliverance of the DNA to heart muscle. Of those steps, the last is the most challenging. In the late 1990s, physicians and physicists hit on the idea of using ultrasound contrast agents to deliver DNA, which can be seen in Figure 8. If the ultrasound is intense enough, the bubbles can burst with sufficient force to breach the membranes of nearby cells. And if the bubbles are coated with DNA, their destruction releases the DNA, enabling it to enter the cells through the holes forced open by the burst.

“Biobots” (a kind of nanorobots), another application of nanotechnology, is the creation of muscle-powered nanoparticles having the ability to transfer information into cells, gives the potential of replacing lost biological function of many tissues such as sinoatrial node. This effect can lead to treatment of diseases which otherwise would be fatal or difficult to cure for human beings

Nanotechnology against Cancer:
Nanotechnology may have an impact on the key challenges in cancer diagnosis and therapy. Diagnosing, treating, and tracking the progress of therapy for each type of cancer has long been a dream among oncologists, and one that has grown closer thanks to parallel revolutions in genomics, proteomics and cell bio1ogy. Nanotechnology’s greatest advantage over conventional therapies may be the ability to combine more than one function. Recently, there is a lot of research going on to design novel nanodevices capable of detecting cancer at its earliest stages, pinpointing it’s location within the human body and delivering chemotherapeutic drugs against malignant cells. The major areas in which nanomedicine is being developed in cancer involve: a) early detection of tumour (developing “smart” collection platforms for simultaneous analysis of cancer-associated markers and designing contrast agents that improve the resolution of tumour area comparing with the nearby normal tissues), and b) cancer treatment (creating nanodevices that can release chemotherapeutic agents). Tumour diagnostics and prevention is the best cure for cancer, but failing that, early detection will greatly increase survival rates with the reasonable assumption that an in situ tumour will be easier to eradicate than one that has metastasized. Nanodevices and especially nanowires can detect cancer-related molecules, contributing to the early diagnosis of tumour. Nanowires having the unique properties of selectivity and specificity, can be designed to sense molecular markers of malignant cells. They are laid down across a microfluidic channel and they allow cells or particles to flow through it. Nanowires can be coated with a probe such as an antibody or oligonucleotide, a short stretch of DNA that can be used to recognize specific RNA sequences. Proteins that bind to the antibody will change the nanowire’s electrical conductance and this can be measured by a detector. As a result, proteins produced by cancer cells can be detected and earlier diagnosis of tumour can be achieved. Nanoparticle contrast agents are being developed for tumor detection purposes. Labeled and non-labeled nanoparticles are already being tested as imaging agents in diagnostic procedures such as nuclear magnetic resonance imaging24. Such nanoparticles are paramagnetic ones, consisting of an inorganic core of iron oxide coated or not with polymers like dextran. There are two main groups of nanoparticles: 1) superparamagnetic iron oxides whose diameter size is greater than 50 nm, 2) ultrasmall superparamagnetic iron oxides whose nanoparticles are smaller than 50nm25. Moreover, quantum dots being the nanoscale crystals of a semiconductor material such as cadmium selenide, can be be used to measure levels of cancer markers such as breast cancer marker Her-2, actin, microfibril proteins and nuclear antigens26. Tumour treatment can be succeeded with nanoscale devices (such as dendrimers, silica-coated micelles, ceramic nanoparticles, liposomes). These devices can serve as targeted drug-delivery vehicles capable of carrying chemotherapeutic agents or therapeutic genes into malignant cells. As an example, a nanoparticle-based drug called “Abraxane”, consisting of paclitaxel conjunctive to protein albumin particles, was approved by the Food and Drug Administration for breast cancer treatment a year ago27. It is worthwhile to mention that selective delivery and targeting of nanoparticles to tumours may overcome the problem of toxicity and may increase the effectiveness of drug delivery. The barriers involving this procedure and that should be under consideration, are a variety of physical and anatomical characteristics of solid tumours, such as the necrotic core with the surrounding hypoxic area, the elevated local temperature and the interstitial liquid pressure. The vascular permeability of the tumour influence the retention of intravenously administered nanoparticles, and the subsequent nanoparticle drug-delivery are shown in Figure 1514,28,29. Several approaches have been used to target nanoparticles to tumour-associated antigens, including direct conjugation of nanoparticles to monoclonal antibodies, modified plasma proteins or viral vectors. Recent progress has been made with targeted viral vectors for gene therapy applications. Figure 16 demonstrates a nanoparticle-delivered EGFP gene (gene coding for Enhanced Green Fluorescent Protein) (green) expressed in a nerve cell (red).

Conclusions
           Nanotechnology in modern medicine and nanomedicine is in infancy, having the potential to change medical research dramatically in the 21st century. Nanomedical devices can be applied for analytical, imaging, detection, diagnostic and therapeutic purposes and procedures, such as targeting cancer, drug delivery, improving cell-material interactions, scaffolds for tissue engineering, and gene delivery systems, and provide innovative opportunities in the fight against incurable diseases.Thanks to nanotechnology tools and techniques, there has been a huge progress on understanding the function of biological structures and their interaction and integration with several non-living systems, but there are still open issues to be answered, mainly related to biocompatibility of the materials and devices which are introduced into the body. Many novel nanoparticles and nanodevices are expected to be used, with an enormous positive impact on human health. The vision is to improve health by enhancing the efficacy and safety of nanosystems and nanodevices. In addition, early diagnosis, implants with improved properties, cancer treatment and minimum invasive treatments for heart disease, diabetes and other diseases are anticipated. In the coming years, nanotechnology will play a key role in the medicine of tomorrow providing revolutionary opportunities for early disease detection, diagnostic and therapeutic procedures to improving health and enhancing human physical abilities, and enabling precise and effective therapy tailored to the patient.
References
1.       Jong WH de, Roszek B., Geertsma R.E., “Nanotechnology in medical applications: possible risks for human health”, RIVM report 265001002, 2005. RIVM, National Institute for Public Health and the Environment, Bilthoven, The Netherlands, 2005
2.       Roszek B, Jong WH de, Geertsma RE. “Nanotechnology for medical applications: state-of-the-art in materials and devices”, RIVM report 265001001, 2005. RIVM, National Institute for Public Health and the Environment, Bilthoven, The Netherlands, 2005
4.       Silva G. A., “Introduction to nanotechnology and its applications to medicine”. Surg Neurol 2004; 61:216
7.       Kane JP, Aouizerat BE. “Novel genetic markers for structural coronary artery disease, myocardial infarction, and familial combined hyperlipidemia: candidate and genome scans of functional SNPs”, Atherosclerosis XIII. Proceedings of the 13th International Atherosclerosis Symposium 2004; 1262:309- 312
8.       Brigger É, Dubernet C, Couvreur P. “Nanoparticles in cancer therapy and diagnosis”. Advanced Drug Delivery Reviews 2002; 54:631-651
9.       Nanomedicine; An ESF – European Medical Research Councils (EMRC) Forward Look report 2005, (www.nanoforum.org)

10.   Bonnemain. “Superparamagnetic agents in magnetic resonance imaging: physiochemical characteristics and clinical applications – a review”. J Drug Target 1998; 6:167-174

Thursday, April 2, 2015

IPL T20 2015

PEPSI IPL 8


The 2015 season of the Indian Premier League (abbreviated as IPL 8 or Pepsi IPL 2015) is the eighth season of the IPL. Kolkata Knight Riders are the defending champions having won the title in the 2014 season. The complete tournament is expected to be held across different cities in India unlike the previous season. The tournament starts on Wednesday, 8 April 2015 after the end of the 2015 Cricket World Cup. A total of 60 T20 matches including Final are expected to be held in the entire tournament.Pepsi IPL 2015 schedule has been revised due to Municipal Elections in Kolkata. No matches in Kolkata from April 12-25 during Municipal Elections.



TEAMS



Changes in IPL 2015 Team Players
    • Parthiv Patel is with Mumbai Indians team now.
    • Manvinder Bisla is with Royal Challengers Bangalore now.
    • Unmukt Chand is with Mumbai Indians.
    • R. Vinay Kumar is with Mumbai Indians too.
Delhi Daredevils have signed former India batsman Pravin Amre as assistant coach from the 2015 season.
  • MS Dhoni (Retained Player)
  • Ravindra Jadeja (Retained Player)
  • Ravichandran Ashwin (Retained Player)
  • Dwayne Bravo (Retained Player)
  • Suresh Raina (Retained Player)
  • Faf Du Plessis
  • Dwayne Smith
  • Brendon McCullum
  • Ashish Nehra
  • Mohit Sharma
  • Ishwar Chandra Pandey
  • Samuel Badree
  • Matt Henry
  • Mithun Manhas
  • Ronit More
  • Baba Aparajith
  • Pawan Negi
  • Michael Hussey
  • Rahul Sharma
  • Kyle Abbott
  • Irfan Pathan
  • Pratyush Singh
  • Ankush Bains
  • Eklavya Dwivedi
  • Andrew Tye
CSK IPL 2015 (Released Players):David Hussey, Ben Hilfenhaus, John Hastings, Vijay Shankar.



  • Shane Watson (Retained Player)
  • James Faulkner (Retained Player)
  • Stuart Binny (Retained Player)
  • Ajinkya Rahane (Retained Player)
  • Sanju Samson (Retained Player)
  • Steven Smith
  • Rajat Bhatia
  • Tim Southee
  • Dhawal Kulkarni
  • Abhishek Nayar
  • Kane Richardson
  • Ben Cutting
  • Karun Nair
  • Unmukt Chand
  • Iqbal Abdullah
  • Deepak Hooda
  • Dishant Yagnik
  • Kevon Cooper
  • Vikramjeet Malik
  • Ankit Nagendra Sharma
  • Rahul Tewatia
  • Pravin Tambe
  • Chris Morris
  • Juan Theron
  • Barinder Singh Saran
  • Dinesh Salunkhe
  • Sagar Trivedi
  • Pardeep Sahu
Rajasthan Royals (Released Players): Amit Mishra, Ankush Bains, Brad Hodge.


  • Shikhar Dhawan (Retained Player)
  • Dale Steyn (Retained Player)
  • David Warner
  • Bhuvneshwar Kumar
  • Karn Sharma
  • Ishant Sharma
  • Moises Henriques
  • KL Rahul
  • Parveez Rasool
  • Naman Ojha
  • Ashish Reddy
  • Ricky Bhui
  • Chama Milind
  • Kevin Pietersen
  • Eoin Morgan
  • Kane Williamson
  • Ravi Bopara
  • Laxmi Ratan Shukla
  • Praveen Kumar
  • Trent Boult
  • Hanuma Vihari
  • Prasanth Padmanabha
  • Siddarth Kaul
Sunrisers Hyderabad (Released Players): Aaron Finch, Amit Mishra, Amit Paunikar, Brendan Taylor, Darren Sammy, Irfan Pathan, Jason Holder, Manprit Juneja, Prasanth Parameswaran, Srikkanth Anirudha, Venugopal Rao.


  • Rohit Sharma (Retained Player)
  • Lasith Malinga (Retained Player)
  • Harbhajan Singh (Retained Player)
  • Ambati Rayudu (Retained Player)
  • Kieron Pollard (Retained Player)
  • Corey Anderson
  • Aditya Tare
  • Jasprit Bumrah
  • Josh Hazlewood
  • Marchant De Lange
  • Pawan Suyal
  • Shreyas Gopal
  • Aaron Finch
  • Pragyan Ojha
  • Mitchell McClenaghan
  • Akshay Wakhare
  • Aiden Blizzard
  • Hardik Pandya
  • Siddhesh Lad
  • J Suchith
  • Nitish Rana
  • Abhimanyu Mithun
Mumbai Indians (Released Players): Michael Hussey, Praveen Kumar, Ben Dunk, Pragyan Ojha, Jalaj Saxena, Krismar Santokie, Sushant Marathe, Apoorv Wankhade, Zaheer Khan, C.M. Gautam.


  • Virat Kohli (Retained Player)
  • Chris Gayle (Retained Player)
  • AB De Villiers (Retained Player)
  • Mitchell Starc
  • Varun Aaron
  • Ashok Dinda
  • Parthiv Patel
  • Nic Maddinson
  • Harshal Patel
  • Vijay Zol
  • Abu Nechim Ahmed
  • Sandeep Warrier
  • Yogesh Takawale
  • Yuzvendra Singh Chahal
  • Dinesh Karthik
  • Subramaniam Badrinath
  • Darren Sammy
  • Sean Abbott
  • Adam Milne
  • David Wiese
  • Jalaj Saxena
  • Sarfaraz Naushad Khan
  • Shishir Bhavane
Royal Challengers Bangalore (Released Players): Albie Morkel, Muttiah Muralitharan, Ravi Rampaul, Sachin Rana, Shadab Jakati, Tanmay Mishra, Yuvraj Singh.


  • Gautam Gambhir (R’etained Player)
  • Sunil Narine (Retained Player)
  • Robin Uthappa
  • Piyush Chawla
  • Yusuf Pathan
  • Shakib Al Hasan
  • Morne Morkel
  • Vinay Kumar
  • Umesh Yadav
  • Manish Pandey
  • Chris Lynn
  • Patrick Cummins
  • Ryan Ten Doeschate
  • Suryakumar Yadav
  • Andre Russell
  • Manvinder Bisla
  • Veer Pratap Singh
  • Kuldeep Singh Yadav
  • James Neesham
  • Brad Hogg
  • Aditya Garhwal
  • Sumit Narwal
  • KC Cariappa
  • Vaibhav Rawal
  • Sheldon Jackson
Kolkata Knight Riders (Released Players): Debabrata Das, Sayan Sekhar Mandal, Jacques Kallis.


  • Manan Vohra (Retained Player)
  • David Miller (Retained Player)
  • Mitchell Johnson
  • Glenn Maxwell
  • George Bailey
  • Virender Sehwag
  • Rishi Dhawan
  • Wriddhiman Saha
  • Shaun Marsh
  • Beuran Hendricks
  • Thisara Perera
  • Gurkirat Singh Mann
  • Sandeep Sharma
  • Mandeep Hardev Singh
  • Akshar Rajesh Patel
  • Parvinder Awana
  • Shardul Narendra Thakur
  • Anureet Singh
  • Shivam Sharma
  • Karanveer Singh
  • Murali Vijay
  • Nikhil Naik
  • Yogesh Golwalkar
Kings XI Punjab (Released Players): Cheteshwar Pujara, Lakshmipathy Balaji, Murali Kartik.


  • Mohammad Shami
  • Nathan Coulter-Nile
  • Quinton De Kock
  • Manoj Tiwary
  • Jean-Paul Duminy
  • Kedar Jadhav
  • Mayank Agarwal
  • Shahbaz Nadeem
  • Saurabh Tiwary
  • Jayant Yadav
  • Milind Kumar
  • Angelo Mathews
  • Yuvraj Singh
  • Amit Mishra
  • Jaydev Unadkat
  • Gurinder Sandhu
  • Shreyas Iyer
  • CM Gautam
  • Dominic Muthuswamy
  • Albie Morkel
  • Travis Head
  • Marcus Stoinis
  • Kona Srikar Bharat
  • KK Jiyaz
  • Zaheer Khan
Delhi Daredevils (Released Players): Dinesh Karthik, HS Sharath, James Neesham, Jaydev Unadkat, Kevin Pietersen, Laxmi Ratan Shukla, Milind Kumar, Murali Vijay, Rahul Sharma, Rahul Shukla, Ross Taylor, Siddarth Kaul, Wayne Parnell.


  Pepsi IPL 8 Full Schedule  2015



MatchDateTeamsVenueTime

Match 1

8th April

Kolkata Knight Riders vs Mumbai Indians

Kolkata

8:00

Match 2
9th AprilChennai Super Kings vs Delhi DaredevilsChennai8:00

Match 3
10th AprilKings XI Punjab vs Rajasthan RoyalsPune8:00

Match 4
11th AprilChennai Super Kings vs Sunrisers HyderabadChennai4:00
Match 511th AprilKolkata Knight Riders vs Royal Challengers BangaloreKolkata8:00
Match 612th AprilDelhi Daredevils vs Rajasthan RoyalsDelhi4:00

Match 7
12th AprilMumbai Indians vs Kings XI PunjabMumbai8:00
Match 813th AprilRoyal Challengers Bangalore vs Sunrisers HyderabadBengaluru8:00
Match 914th AprilRajasthan Royals vs Mumbai IndiansAhemdabad4:00
Match 1014th AprilKolkata Knight Riders vs Chennai Super KingsKolkata8:00
Match 1115th AprilKings XI Punjab vs Delhi DaredevilsPune8:00
Match 1216th AprilSunrisers Hyderabad vs Rajasthan RoyalsVishakhapatnam8:00
Match 1317th AprilMumbai Indians vs Chennai Super KingsMumbai8:00
Match 1418th AprilSunrisers Hyderabad vs Delhi DaredevilsVishakhapatnam4:00
Match 1518th AprilKings XI Punjab vs Kolkata Knight RidersPune8:00
Match 1619th AprilRajasthan Royals vs Chennai Super KingsAhemdabad4:00
Match 1719th AprilRoyal Challengers Bangalore vs Mumbai IndiansBengaluru8:00
Match 1820th AprilDelhi Daredevils vs Kolkata Knight RidersDelhi8:00
Match 1921st AprilRajasthan Royals vs Kings XI PunjabAhemdabad8:00
Match 2022th AprilSunrisers Hyderabad vs Kolkata Knight RidersVishakhapatnam4:00
Match 2122nd AprilRoyal Challengers Bangalore vs Chennai Super KingsBengaluru8:00
Match 2223th AprilDelhi Daredevils vs Mumbai IndiansDelhi8:00
Match 2324th AprilRajasthan Royals vs Royal Challengers BangaloreAhemdabad8:00
Match 2425th AprilMumbai Indians vs Sunrisers HyderabadMumbai4:00
Match 2525th AprilChennai Super Kings vs Kings XI PunjabChennai8:00
Match 2626th AprilKolkata Knight Riders vs Rajasthan RoyalsKolkata4:00
Match 2726th AprilDelhi Daredevils vs Royal Challengers BangaloreDelhi8:00
Match 2827th AprilKings XI Punjab vs Sunrisers HyderabadMohali8:00
Match 2928th AprilKolkata Knight Riders vs Delhi DaredevilsKolkata8:00
Match 3029th AprilRoyal Challengers Bangalore vs Rajasthan RoyalsBengaluru8:00
Match 3130th AprilChennai Super Kings vs Kolkata Knight RidersChennai8:00
Match 321st MayDelhi Daredevils vs Kings XI PunjabDelhi4:00
Match 331st MayMumbai Indians vs Rajasthan RoyalsMumbai8:00
Match 342nd MayRoyal Challengers Bangalore vs Kolkata Knight RidersBengaluru4:00
Match 352nd MaySunrisers Hyderabad vs Chennai Super KingsHyderabad8:00
Match 363rd MAyKings XI Punjab vs Mumbai IndiansMohali4:00
Match 373rd MayRajasthan Royals vs Delhi DaredevilsTBC8:00
Match 384th MayChennai Super Kings vs Royal Challengers BangaloreChennai4:00
Match 394th MayKolkata Knight Riders vs Sunrisers HyderabadKolkata8:00
Match 405th MAyMumbai Indians vs Delhi DaredevilsMumbai8:00
Match 416th MayRoyal Challengers Bangalore vs Kings XI PunjabBengaluru8:00
Match 427th MayRajasthan Royals vs Sunrisers HyderabadTBC8:00
Match 438th MayChennai Super Kings vs Mumbai IndiansChennai8:00
Match 449th MayKolkata Knight Riders vs Kings XI PunjabKolkata4:00
Match 459th MayDelhi Daredevils vs Sunrisers HyderabadRaipur8:00
Match 4610th MayMumbai Indians vs Royal Challengers BangaloreMumbai4:00
Match 4710th MayChennai Super Kings vs Rajasthan RoyalsChennai8:00
Match 4811th MaySunrisers Hyderabad vs Kings XI PunjabHyderabad8:00
Match 4912th MayDelhi Daredevils vs Chennai Super KingsRaipur8:00
Match 5013th MayKings XI Punjab vs Royal Challengers BangaloreMohali8:00
Match 5114th MayMumbai Indians vs Kolkata Knight RidersMumbai8:00
Match 5215th MaySunrisers Hyderabad vs Royal Challengers BangaloreHyderabad8:00
Match 5316th MayKings XI Punjab vs Chennai Super KingsMohali4:00
Match 5416th MayRajasthan Royals vs Kolkata Knight RidersTBC8:00
Match 5517th MayRoyal Challengers Bangalore vs Delhi DaredevilsBengaluru4:00
Match 5617th MaySunrisers Hyderabad vs Mumbai IndiansHyderabad8:00
Qualifier 119th MayTBD vs TBDTBC8:00
Eliminator20th MayTBD vs TBDTBC8:00
Qualifier 222nd MayTBD vs TBDTBC8:00
Final24th MayTBD vs TBDKolkata8:00