Nanotechnology & Nanomedicine

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1 Nanotechnology & Nanomedicine Hans Bluyssen,

2 Nanorobot Sending the sperms

3 Nanorobot Seeking cancer cell

4 Nanorobotic Artery Cleaner

5 Nanorobot repairing nerve cell

6 Ability to enter cells and correct DNA or a deficiency. Repair cells, tissue, and even organs. Carry tiny cameras and be powered from the electrolytes in the blood. Break up blood clots or even kidney stones.

7 Nanotechnology Engineering and manufacturing at the scale of a nanometer or nanoscale (nanometer = 10-9 meter), a hundredthousandth the width of a human hair. Examples of nano-substance are- Atom diameter 0.15 nm, diameter of double strand DNA 2 nm, and cell nm.

8 ww.mathworks.com What is Nanoscale Fullerenes C 60 12,756 Km m 22 cm 0.7 nm 0.22 m m 10 millions times smaller 1 billion times smaller

9 Carbon Nanotube Fullerenes

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11 Nanotechnology Creation of functional devices in the nanometre range and the exploitation of the unique properties of these devices in various fields

12 Compared to Human Hair A Human Hair is about 100,000nm wide

13 Where all the action is: the cell (10-30 um)! Cells themselves are very complex and efficient nanomachines. Most areas of nanoscience aim to learn from biological nanosystems.

14 Watering flowers or flooding the neighborhood? treating atherosclerosis with lipid lowering drugs arteriosclerosis: - begins at the cell - > focal lesions in the arteries - leads to myocardial infarction and stroke some lipid lowering drugs: arterial plaque effects on plaques can save lives effects on immune system!!!!!solution: Nanomedicine effects on liver muscles: can lead to cell death can endanger human life Can endanger large companies

15 Nanobiotechnology Science s growing ability to work at the molecular level, atom by atom, combining biological materials and the rules of physics, chemistry, and genetics to fabricate minute synthetic structures. Nanomanufacturing? The ultimate goal is to develop a highly functional system of biosensors, electronic circuits, nanosized microchips, molecular switches, and even tissue analogs for growing skin, bones, muscle, and other organs of the body.

16 Nanomedicine The application of nanotechnology to disease treatment, diagnosis, monitoring, control of biological systems

17 NANOTECHNOLOGY TOOL BOX NANOPORES NANOPARTICLES NANOFIBERS NANOELECTRONICS NANOCANTILEVERS NANORIBBONS NANOCOMPOSITES NANOTUBES NANOCRYSTALS NANOARRAYS NANOPROBES NANOSHELLS NANOCOATINGS BUCKYBALLS

18 Drug encapsulation and delivery with nanoparticles Vehicles for delivery: - coated solid particles - vesicles - liposomes - micelles - polymers - solid lipid nanoparticles - silica nanoparticles

19 Nanoparticles 8 Re F, Moresco R, Masserini M. Nanoparticles for neuroimaging. Journal of Physics D: Applied Physics. 2012;45(7):

20 Nanomedicine A vehicle for delivery of therapeutics into the body Functionalized nanoparticles Small molecule drug compounds, DNA/genes, proteins, vaccines, etc. Administration routes to reach systemic circulation or infected organs and cells: oral, intravenous, inhalation, ocular, topical

21 Nanoparticle as delivery system for drugs or genes for tissue and cell Functionalized nanoparticles

22 Silica nanocapsules Porous hollow silica nanocapsules

23 Nanoparticles/nanocapsules as drug delivery carriers to cancer Functionalized nanoparticles Porous hollow silica nanocapsules for Cefradine delivery (antibacterial chemical)

24 The goal of nanomedicine is to develop safer and more effective therapeutic and diagnostic modalities Functionalized nanoparticles McNeil SE. J Leukoc Biol, (3): p doi: /jlb

25 Interesting facts about nanomedicine A. Interest in the area has grown exponentially B. Drug delivery is the most productive area C. Drug delivery is the most established technology in the nanomedicine market Nature Biotechnology 2006, Vol. 4, pp

26 Nanoparticles and Drug delivery Drug targeting by nanoparticles or nanocapsules offers the following enormous advantages: -reduces dosage, ensures the pharmaceutical effects, and minimizes side-effects; -protects drugs against degradation and enhances drug stability. Nanoparticles can penetrate through small capillaries and are taken up by cells, which allows efficient drug accumulation at target sites. A sustained and controlled release of drugs at target sites over a period of days or even weeks is possible.

27 Nanoparticles and Drug delivery Nanoparticles with diameter less than 200nm are not screened out of circulation by liver and spleen. Nanotech based drug delivery is less toxic as well as inexpensive.

28 Trafficking of nanoparticles Nanoparticles eventually act as reservoirs for sustained release of encapsulated therapeutic agent at target cells. -Intracellular -Extracellular

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30 Nanoparticle use in Cancer Treatments Because of their small size, nanoparticles can pass through interstitial spaces between necrotic and quiescent cells. Tumor cells typically have larger interstitial spaces than healthy cells Particles collect in center bringing therapeutics to kill the tumor from inside out.

31 Nanotechnology in Health Care Thermal ablation of cancer cells Nanoshells have metallic outer layer and silica core Selectively targeted to cancer cells The nanoshells are heated with an external energy source killing the cancer cells Thermal ablation of cancer cells assisted by nanoshells coated with metallic layer and an external energy source National Cancer Institute

32 Drug Delivery Because of their small sizes, nanoparticles are taken up by cells where large particles would be excluded or cleared from the body ) A nanoparticle carries the pharmaceutical agent inside its core, while its shell is functionalized with a binding agent 2) Through the binding agent, the targeted nanoparticle recognizes the target cell. The functionalized nanoparticle shell interacts with the cell membrane 3) The nanoparticle is ingested inside the cell, and interacts with the biomolecules inside the cell 4) The nanoparticle particles breaks, and the pharmaceutical agent is released Source: Comprehensive Cancer Center Ohio University

33 A Drug Delivery Nanoparticle A. Nanoparticles for drug delivery can be metal-, polymer-, or lipid-based. Below (left) an example of the latter, containing SiRNA encapsulated, and functionalized with a specific antibody. SiRNA can control often lethal inflammatory body responses, as shown in the microscopic images below (right) B. C. antibody lipid SiRNA Healthy tissue Sick tissue treated with non-targeted nanoparticles Science 2008, Vol. 316, pp Sick tissue treated with targeted nanoparticles

34 Dendrimers Dendritic polymers = Dendrimers Polyamidoamine (PAMAM) phosphorous-based, Polylysine Highly branched structures Molecular hooks to attach Cell identification tags, fluorescent dyes, enzymes ideal building blocks in nanochemistry for the creation of more complex three-dimensional structures.

35 Dendrimers & Therapeutics The Michigan Nanotechnology Institute for Medicine and Biological Sciences

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37 What are Quantum Dots? At the heart of the fluorescence of Qdot nanocrystals is the formation of excitons. The exciton can be thought of as analogous to the excited state of traditional fluorophores; however, excitons typically have much longer lifetimes (up to ~µseconds). Qdot nanocrystals are also extremely efficient machines for generating fluorescence; their intrinsic brightness is often many times that observed for other classes of fluorophores. Another practical benefit is that the photostability of Qdot nanocrystals is many orders of magnitude greater than that associated with traditional fluorescent molecules; enables longterm imaging experiments.

38 widely exploited in the development of multicolor assays Tuneability of Qdot nanocrystals. Five different nanocrystal solutions are shown excited with the same long-wavelength UV lamp; the size of the nanocrystal determines the color.

39 Quantum Dot Bioconjugate Qdot bioconjugate is a generic term to describe Qdot nanocrystals coupled to proteins, oligonucleotides, small molecules, etc., which are used to direct binding of the quantum dots to targets of interest.

40 Laminin in a mouse kidney section was labeled with an anti-laminin primary antibody and visualized using greenfluorescent Qdot 565 IgG. PECAM (platelet/endothelial cell adhesion molecule; CD31) was labeled with an anti PECAM-1 primary antibody and visualized using red-fluorescent Qdot 655 IgG. Nuclei were stained with blue-fluorescent Hoechst

41 Targeting QD s for intracellular imaging A. Using a drug-delivery-like mechanism, a targeted lipid-based nanoparticle (TNP) encapsulating QD s specifically attacks a cell having the receptors that pair with its ligand coating. Upon ingestion and destruction of the TNP, the QD s are set free and accumulate on intracellular structures B. Ligand coated QDNC Ingestion Decomposition C. QD (red)intracellular uptake is enhanced when using the QDNC instead of the free QD s labeling QD release Nano Letters 2008., Vol. 8, pp D. Imaging of nucleus (blue) and cytoplasm (other) after 30 min (left) and 3 hours after uptake

42 Water soluble quantum dots to image sentinel lymph nodes which are used for diagnosing breast cancer. Antibody-Modified Quantum dots for the sensitive imaging of the tumour tissue on a tumour-bearing mouse.

43 QD Localization of a Tumor It is possible to overlap X-ray images with infrared images to localize a tumor. Anatomical context + QD s emission: tumor location. Annu. Rev. Biomed. Eng Vol. 9, pp

44 Diagnosis A. Detection of multiple biomarkers simultaneously B. A specific phenotype of cancer cells has a particular combination of biomarkers on its membrane C. Different phenotypes show different aggressiveness on their metastatic behavior D. Blood vessels tumor Cancer cells Source: metastasis

45 Multiplex Diagnosis A. Four quantum dots of different diameter (i.e. different color) are respectively functionalized with four different antigens. Allowing for the distinction of two distinct phenotypes The peak intensity correlates to the concentration of a specific QD As a result cancer cells of different phenotype are colored differently Aggressive cancer cells Each peak correspond to the emission of a specific QD/antigen Mild cancer cells Nature Protocols Vol. 2, pp. 1-15

46 Nanotech in Disease Imaging & Therapeutic Monitoring in vivo imaging system including the relationship between metastasis of cancer and the onset of angiogenesis and the efficiency of anticancer drugs.

47 Imaging

48 Diagnosis using Nanothermometers Cancer cells appears to have a more elevated temperature than normal cells. Therefore, a local temperature mapping can be used to determine the spread of a tumor A gold nanoparticle is functionalized with a PEG coating, which itself is assembled to a layer of smaller QD s. The emission properties of the nanoparticle change with temperature due to the stretching/contraction of the PEG healthy sick Thermal image of a healthy and cancerous breast Source: 9th European Congress of Thermology, Krakow, Poland Angew. Chem. Int. Ed. 2005, Vol. 44,

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62 Lab-on-a-Chip One of the more promising areas of nanofluidics is its potential for integration into microfluidic systems, i.e. MicroTotal Analytical Systems or Lab-on-a-chip structures Credits: Mathies Lab, UC-Berkeley Quake Lab, Stanford Agilent, Inc.

63 Lab-on-a-Chip

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65 Lab-on-Chip in Health Care Detection and Diagnosis Lab on chips help detection and diagnosis of diseases more efficiently Nanowire and cantilever lab on chips help in early detection of cancer biomarkers The microfluidic channel with nanowire sensor can detect the presence of altered genes associated with cancer J. Heath, Cali. Insti. of Technology The nanoscale cantilever detects the presence and concentration of various molecular expressions of a cancer cell A. Majumdar, Univ. of Cal. at Berkeley

66 BioCOM Chip Three cantilevers coated with three different antibodies, are exposed to prostate-specific antigen (PSA) The left cantilever bends as PSA binds to the anti-psa antibody on the cantilever The other cantilevers do not bend because their antibodies do not bind to PSA. Min Yue, Katherine Dunphy, Henry Lin, Srinath Satyanarayana (

67 Diagnostics Biosensors Novel Materials Antigen Antibody Electrode ZnO nanowires Ultra-sensitive biosensor for the detection of bio-markers using bio-compatible ZnO nanowires.

68 BioMEMS Micro and Nanofluidics

69 The Not-so-Distant Future 2008 PDA?? Paramount

70 Lab-on-a-Pill

71 Today

72 From Housecalls to House Calls

73 Tomorrow

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75 Nanotechnology & Medicine: Future Patients will drink fluids containing nanorobots programmed to attack and reconstruct the molecular structure of cancer cells and viruses. Nanorobots could also be programmed to perform delicate surgeries: nano-surgeons Additionally, nanorobots could change your physical appearance: nano-cosmetics

76 CONCEPTIONS OF A FANTASTIC FUTURE FOR NANOMEDICINE NANOBOTS TO CLEAN ARTERIES NANOHUMVEES TO DESTROY TUMOR CELLS

77 Respirocyte The artificial red blood cell or "respirocyte Blood borne spherical 1-micron diamondoid 1000-atm pressure vessel with active pumping powered by endogenous serum glucose, able to deliver 236 times more oxygen to the tissues per unit volume than natural red cells and to manage carbonic acidity

78 Respirocyte An onboard nanocomputer and numerous chemical and pressure sensors enable complex device behaviors remotely reprogrammable by the physician via externally applied acoustic signals. Primary applications will include -Transfusable blood substitution; -Partial treatment for anemia, -Perinatal/neonatal and lung disorders; -Enhancement of cardiovascular/neurovascular procedures, -Tumor therapies and diagnostics; -Artificial breathing; and -A variety of sports.

79 Artificial platelets (Clottocyte) An artificial mechanical platelet appears to halt bleeding times faster than natural hemostasis. A single clottocyte, upon reliably detecting a blood vessel break, can rapidly communicate this fact to its neighbors, immediately triggering a progressive controlled mesh-release cascade.

80 Vasculoid The vasculoid is a single, complex, multisegmented nanotechnological medical robotic system capable of duplicating all essential thermal and biochemical transport functions of the blood, including circulation of respiratory gases, glucose, hormones, cytokines, waste products, and cellular components. This nanorobotic system, a very aggressive and physiologically intrusive macroscale nanomedical device comprised of ~500 trillion stored or active individual nanorobots, weighs ~2 kg and consumes from watts of power in the basic human model, depending on activity level. The vasculoid system conforms to the shape of existing blood vessels and serves as a complete replacement for natural blood.

81 Augmentation Nanomedicine can make possible the re-engineering of the human body, including the improvement of existing natural biological systems and the addition of new systems and capabilities not found in nature. Such reengineering is commonly called "augmentation".

82 Goals of Nanomedicine Ultimate goal is to integrate detection, diagnostics, treatment and prevention of disease into a personalized single platform

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84 Potential problems of nanotechnology in medicine Influenza viruses kills 10 Mio people during world war I Computer virus shoots down millions of PC s worldwide in year Autonomous, self-replicating nano-agents: a danger for the future?

85 Nanotechnology Applications Information Technology Smaller, faster, more energy efficient and powerful computing and other IT-based systems Medicine Cancer treatment Bone treatment Drug delivery Appetite control Drug development Medical tools Diagnostic tests Imaging Energy More efficient and cost effective technologies for energy production Solar cells Fuel cells Batteries Bio fuels Consumer Goods Foods and beverages Advanced packaging materials, sensors, and lab-on-chips for food quality testing Appliances and textiles Stain proof, water proof and wrinkle free textiles Household and cosmetics Self-cleaning and scratch free products, paints, and better cosmetics

86 About $80B in products incorporate nanotechnology in the US in 2009 with the leading category being: Consumer Products

87 Sporting Goods

88 Cosmetics, Clothes and Food

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90 This is a 2 gigabyte hard drive. It weighs about 70 pounds. It was first used in the 1980s. Its cost at that time ranged from $80,000 to $140,000. Image by HighPoint Learning

91 2 GB in 1980s $80,000 2 GB in 1990s $200 Image by HighPoint Learning 2 GB in 2010 $5

92 Image by HighPoint Learning Current research shows that by using nanotechnology, 1000 GB of memory can fit on the head of this pin GB is 1 Terabyte.

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94 Nanomanufacturing Nanomanufacturing is the use of mechanical, chemical, or alternative physical processes at the nano-level level to directly create, or indirectly direct the crystalline merger of, atoms and micro-scale materials into multi-faceted materials and inventions. These materials incorporate nanoparticles, nanoshells, nanopolymers, nanotubes, nanoctagons and nanowires.

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96 Molecular manufacturing As millions of atoms are pieced together by nanomachines, a specific product will begin to take shape. The goal of molecular manufacturing is to manipulate atoms individually and place them in a pattern to produce a desired structure.

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98 Economic Impact of Nanotechnology Market Size Predictions (within a decade)* $340B/yr Materials $300B/yr Electronics $180B/yr Pharmaceuticals $100B/yr Chemical manufacture $ 70B/yr Aerospace $ 20B/yr Tools $ 30B/yr Improved healthcare $ 45B/yr Sustainability $1 Trillion per year by 2015 *2007 Estimates by industry groups, source: NSF

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