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Transcript of Medical Technology
http://www.nanotechproject.org/inventories/medicine/apps/ Copyright April 2009 The Pennsylvania State University Reproduced with permission of Nanogen®, Inc. Reproduced with permission of Nanogen®, Inc. An example of an early generation commercially available “NanoChip®” Selected DNA probe strands are placed on the different pads on a “chip”. If some complimentary strand in the sample binds at a particular site, that particular DNA, which is a hallmark of a specific defect or disease, must be present in the sample. Array Detection Technology Copyright April 2009 The Pennsylvania State University Courtesy: Omid Farokhzad, M.D., Brigham and Women’s Hospital – Harvard Medical School Example: Drug Bearing Nanoparticle Functionalized for Targeted Binding to Tumor and for Controlled Solubility
Graphical representation of docetaxel-encapsulated nanoparticles
Scanning electron-microscopy (SEM) image of docetaxel-encapsulated nanoparticles. The average particle size is approximately 150 nanometers in diameter Courtesy of CNEU Copyright April 2009 The Pennsylvania State University The ligands (green triangles) on the surface of the
nanoparticle fit into the cell receptors, allowing encapsulated
drug molecules to enter the tumor cell after binding. Active Tumor Targeting
by Nanoparticles Copyright April 2009 The Pennsylvania State University As Sophisticated as Assisting
In Cancer Surgery
Quantum dots are being explored for their use in tracking cancer cell movement in the lymph system.
QDs are injected into a tumor and then their migration to a lymph node is monitored using QD fluorescence.
Without this tool, a surgeon does not know which lymph node may contain cancerous cells and so must take out many nodes greatly complicating the surgery. Copyright April 2009 The Pennsylvania State University ANTIBACTERIAL DRESSINGS:
For years, silver has been used as an antibacterial agent. But in nanoparticle form, due to the large surface to volume ratio, it kills bacteria much faster thereby reducing inflammation.
Nanocrystalline silver is now embedded in burn and wound dressings prescribed by doctors or used by clinics. As Straightforward as Better Bandages Copyright April 2009 The Pennsylvania State University Each functionalized to attach (“stick”) to a different type of tumor. As can be seen from the pictures below, different QD’s with different functionalization can be made to go to different types of tumors and then be used for Fluorescence Imaging of the tumors. Yezhelyev, Emerging use of nanoparticles in diagnosis and treatment of cancer Fluorescent Nanoparticles Copyright April 2009 The Pennsylvania State University Such Functionalized
Can be Used for
Quantum Dot Fluorescence Imaging of Tumors From Dr. R. Rezka, MDC, Berlin Copyright April 2009 The Pennsylvania State University Molecules are attached to the nanoparticl so it sticks to only cancer cells 3D Model of a Functionalized Nanoparticle Copyright April 2009 The Pennsylvania State University Quantum Dot Fluorescence
Functionalized Nanoparticles Copyright April 2009 The Pennsylvania State University Contrast agents, injected into patients undergoing MRI, affect the proton spin relaxation process. This in turn boosts the intensity of the MRI signal used to create an image
Magnetically active nano-particles can make excellent contrast agents and make MRI scanning even more powerful in disease detction Quick Look at How MRI Works Radio frequency (RF) photons can promote protons from the lower spin energy to the higher spin energy
The manner in which the more energetic protons lose their extra energy is called relaxation. During relaxation, radiation is emitted back out from the sample (which may be you) permitting imaging with this emitted RF radiation Copyright April 2009 The Pennsylvania State University Magnetic Resonance Imaging (MRI) Source: http://www.wikipedia.org/ Magnetic resonance imaging (MRI)
is a non-invasive method used to render images of the inside of an object. MRI also has many uses outside of the medical field. In medical applications, MRI is best suited for imaging non-calcified tissue. Copyright April 2009 The Pennsylvania State University MRI Imaging Copyright April 2009 The Pennsylvania State University Click on the image to view the movie Lidke, D. S.; Jovin, T. M., et al. Nature Biotech. 2004, 22, 198 Using Nanotechnology to
Study Cancer Cell Structure Hela cancer cells, genetically engineered so that protein in EGF receptor fluoresces in the green, are seen to be taking up the human growth peptide EGF. The EFG is tagged in the movie with red-fluorescing quantum dots so we can follow its movement. It was not known that EGF receptors are positioned out on such extended filopodia in at least some cancer cells. This is not the case in normal cells.
Copyright April 2009 The Pennsylvania State University Cancer Cell Structure Copyright April 2009 The Pennsylvania State University Cancer Cell Multiplication Copyright April 2009 The Pennsylvania State University Arnold Seitz & Thomas Surrey, European Molecular Biology Lab, Hidelberg, Gr. We watch Kineasine Molecules labeled using Quantum Dots as they move on Microtubules Here the kineasine molecules have been labeled with green-emitting QDs so we can see them moving. Note kineasine sometimes stops, then restarts as it moves along the microtubule tracks. Using Nanotechnology to
watch Cell Nano-machinery Copyright April 2009 The Pennsylvania State University Here a quantum dot (red circular structure) in the top set of pictures is compared to the flurophore Alexa 488 dye molecule (green circular structure). Both are being illuminated with a 100 Watt Mercury lamp excitation to cause the red and green fluorescence, respectively. As can be seen, the fluorophore quick loses its ability to fluoresce; i.e., it bleaches within 100 seconds. The QD does not bleach. Quantum Dot Fluorescence Copyright April 2009 The Pennsylvania State University
We can watch things move in a cell by attaching either fluorophores or quantum dots to the machinery. This attaching is called “tagging”. Both Fluorophores and Quantum Dots fluoresce (give off light when illuminated). Fluorophores are molecules and quantum dots are man-made nano-particles.
Fluorphores quickly lose their ability to give off light. This is called bleaching.
Quantum dots have the tremendous advantage of not bleaching! Watching the
Intra-cell Machinery Copyright April 2009 The Pennsylvania State University Cell Machinery: Microtubules and Actin Public Library of Science, “The Intersection of Biology and Materials Science” by George M. Whitesides and Amy P. Wong Vol. 31, p. 23, January 2006 Copyright April 2009 The Pennsylvania State University Molecular machines and organelles:
The ultimate in functional nanosystems -’biological nanomachines’ -populate the cell.
These “machines” include flagellar micromotor of bacteria, linear micromotors of muscle and of the microtubules that organize and move the cell, voltage-gated ion channels, DNA replication complexes, and multimeric membrane receptors. These and countless other structures in the cell, are astonishingly complex. “The ‘right”size in nanobiotechnology”, G. M. Whitesides NATURE BIOTECHNOLOGY, Volume 21, Number 10, October 2003 Molecular Machines in Cells Copyright April 2009 The Pennsylvania State University The Workings of
Intra-cellular Machinery Copyright April 2009 The Pennsylvania State University The Lotus Leaf Copyright April 2009 The Pennsylvania State University This module is one of a series designed to be used by faculty members at post-secondary institutions in workshops, courses, and overview lectures to introduce nanotechnology and its applications. There is no particular significance to the module number system
The series was funded in part by:
The National Science Foundation
Grant # DUE 0532646 and DUE 0802498
The Pennsylvania Department of Community and Economic Development
Grant # C000029471 and C000036659
Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Science Foundation or the Pennsylvania Department of Community and Economic Development Copyright April 2009 The Pennsylvania State University © patton brothers illustration (www.pattonbros.com) Nanotechnology is Impacting Everything
Nanotechnology, Biology, and Medicine Introduction to Nanotechnology
Module # 9 Copyright April 2009 The Pennsylvania State University This module, produced by the Center for Nanotechnology Education and Utilization at
The Pennsylvania State University,
is one of a series developed to introduce nanotechnology and its applications to a broad audience. Each module, its component viewgraphs, and the companion glossary are copyrighted 2009 by
The Pennsylvania State University.
All rights reserved. © 2005-2009 Nanogen, Inc Copyright April 2009 The Pennsylvania State University Cellomic’s micro-cell array system Aclara’s variety of Microfluidic platforms Agilent’s Lab-on-a-Chip and Microarray technology Some Companies Currently Producing Products with this Technology Copyright April 2009 The Pennsylvania State University Courtesy: Omid Farokhzad, M.D., Brigham and Women’s Hospital – Harvard Medical School Some Results Untreated Docetaxel-
nanoparticles Docetaxel –
nanoparticles Docetaxel alone Representative mouse at end point (109 days) for each group is shown (left) alongside images of excised tumors (right). For the docetaxel targeted nanoparticle group, which achieved complete tumor regression, the scar tissue and underlying skin at the site of injection are shown. Black arrows point to the position of the implanted tumor on each mouse. Copyright © 2005 by Dalhousie University. Copyright © 2005 by Dalhousie University. Copyright April 2009 The Pennsylvania State University Liposomes fuse with target cell
membranes leading to increased
intracellular delivery of liposome cargo. Liposome Nanoparticles for
Drug Delivery Copyright April 2009 The Pennsylvania State University
Many different types of Nanoparticles are being explored for drug delivery. Several types are already in FDA approved use.
Nanoparticles can be functionalized to attach to only certain types of cells giving targeted drug delivery.
Nanoparticles can be functionalized to be soluble in body fluids obviating drug insolubility problems. Nanoparticles for Drug Delivery Copyright April 2009 The Pennsylvania State University Kim et al. Nature Biotech. Vol. 22, pp. 93 (2004)
In this picture,near-infra-red fluorescing quantum dots have been injected into a primary tumor (large greenish-yellowish region at right) in a near-human sized pig. Light from the infra-red part of the electro-magnetic spectrum is used to excite the QD’s into fluorescing in the infra-red. Infra-red is used since it can penetrate tissue. However, the human eye can not see infra-red so a computer is used to convert the infra-red image into the false-color image seen. This image clearly shows transport of the tiny quantum dots from the tumor through lymph vessels to a nearby lymph node (smaller green area at left) even when imaged non-invasively through the skin. This use of quantum dots allows a surgeon to see the tumor, to see how cancer cells may be moving in the lymph system, and to determine which lymph nodes should be removed. An Example: Tracking Cancer Cell Movement Copyright April 2009 The Pennsylvania State University Courtesy: Moriel NessAiver, Ph.D. Simply Physics, Baltimore MD MRI uses the fact that
protons act like tiny
magnets with “north and south
poles”. This tiny magnet property
is called “spin”. It is a quantum
When an external
magnetic field is present,
as it is in an MRI scanner,
the spin of each proton either
aligns with or against the
external magnetic field How MRI Works Copyright April 2009 The Pennsylvania State University Click on the image to view the movie Lagerholm, B.C., et al. Nano Letters 2004, 4 In this movie, we watch cancer cells labeled with red-emitting Quantum Dots (QDs). Because the OD’s don’t bleach, this movie is able to allow us watch the cells for three hours.
Notice that in this (much speeded-up) three hour period some cells multiply several times Using Nanotechnology to
Study Cancer Cell Multiplication Copyright April 2009 The Pennsylvania State University Watching Some of the Nano-scale Machinery in a Cell Ahmet Yildiz, Joseph N. Forkey, Sean A. McKinney, Taekjip Ha, Yale E. Goldman, Paul R. Selvin: Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging with 1.5-nm Localization. Science. 2003. Vol. 300. p.2061 Myosin V (green), a cellular motor protein, carries cargo within cells by moving along actin filaments (red). It takes 37 nanometer steps by placing one “foot” over the other, as revealed by a fluorophore tag (rainbow-colored oval). [Illustration:PrecisionGraphics.com} Copyright Lotus Effect ® Copyright Lotus Effect ® Copyright April 2009 The Pennsylvania State University
Tools exist to “see” that the Lotus leaf has a nano-textured surface covered with wax nano crystals that makes the surface hydrophobic (i.e., water repelling). Forces water to bead up on the surface. How the
Lotus Leaf Works Copyright April 2009 The Pennsylvania State University Click on the black box to view the movie National Cancer Institute, NIH
What’s being done in Cancer Research Reflects the Across-the-Board Impact of Nanotechnology in Biology and Medicine Courtesy Andy Kessler Copyright April 2009 The Pennsylvania State University Andy Kessler - Nanotechnology and "The End of Medicine" Nanotechnology, Detection, and the Medicine of the Future © 2007 Medical Research Council Copyright April 2009 The Pennsylvania State University Various probes such as known antibodies or DNA strands can be fixed to these pads. If target antigens or complimentary strands of DNA pass-by in a sample, then they’ll attach at the corresponding probe site. If they are tagged with a QD, for example, their presence is detected by the fluorescence seen above. In other words, if a certain physical position on the chip fluoresces, you know a certain antigen or DNA strand is present in the sample. Array Detection Technology Courtesy of Dr. Krystof Bankiewicz, University of California, San Francisco Copyright April 2009 The Pennsylvania State University http://nano.cancer.gov/news_center/nanotech_news_2006-01-09b.asp Real-time magnetic resonance image showing the enhancement produced
by a gadolinium nanoparticle formulation diffusing through a small region of the brain. An Example of Nanoparticle
MRI Imaging Copyright April 2009 The Pennsylvania State University University of Illinois at Urbana-Champaign.The Imaging Technology Group,05 North Mathews, Urbana IL 61801 USA Actin filaments (red) and Microtubules (green) Microtubules (green) in a cultured epithelial cell. It also shows actin (red) filaments. Microtubules provide structural support and the "tracks" or “highways” along which intracellular products are carried. Actin filaments are mainly structural elements but do play a “highway” role too. The cells were treated with fluorophores to visualize the microtubules and the actin. A Real Picture of Microtubules and Actin in a Cell Scanning Electron Microscope image of nano-structures on leaf surface http://www.youtube.com/watch?v=SADr7ByM2-s&feature=player_detailpage When the leaf tilts, gravity causes the droplet to roll off, thereby cleaning the leaf surface. Using stamping, arrays of pads can be constructed on a chip.