Nanotechnology & Nanobiotechnology (Global Science, Engineering and Business Perspectives) by
ABSTRACT • An overview of recent scientific and engineering advances of nanotechnology and nanobiotechnology and their global scientific and business prospects.
G.Ali Mansoori (
[email protected])
BioEngineering, Chemical Engineering & Physics Departments
• My research on design of nanoparticles, nanoclusters, nanoconjugates and molecular building blocks and their applications in science, engineering and health.
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NORTHERN ILLINOIS UNIVERSITY February 12, 2010
What is nanotechnology? According to the US National Science and Technology Council “The essence of nanotechnology is the ability to work at the molecular level, atom by atom, to create large structures with fundamentally new molecular organization. The aim is to exploit these properties by gaining g g control of structures and devices at atomic,, molecular, and supramolecular levels and to learn to efficiently manufacture and use these devices”.
Our Courses at UIC BioE 405: Atomic & Molecular Nanotechnology www.uic.edu/classes/bioe/bioe405 3 OR 4 hours. Nanoscale structures and phenomena. Simulation methods for nano systems, and molecular assemblies. Molecular building blocks, scanning probe and atomic force microscopy, quantum mechanical phenomena. 3 undergraduate hours. 4 graduate hours. Prerequisite(s): Senior standing or above. Recommended background: Engineering or physical science major. major
BioE 505: NanoBioTechnology www.uic.edu/classes/bioe/bioe505
Nanobiotechnology: Nanotechnology + Life Sciences
Major Advancements
4 hours. Nanotechnology theory and applications in biology and medicine. Molecular simulations, combinatorial chemistry. Nanoscale structures, molecular building blocks, integrated nano-bio complexes. Positional and self-assembly, self-replication. Recommended background: Engineering or physical sciences
Major Advancements STM in 1981 & AFM in 1986
Richard P. Feynman, Physics Nobel Laureate, is credited with the birth of nanotechnology. 1959 Challenged the scientific community : “There’s There s no question that there is enough room on the head of a pin to put all of the Encyclopedia Britannica,… I’m not inventing antigravity, which is possible someday only if the laws are not what we think. I am telling what could be done if the laws are what we think; we are not doing it simply because we haven’t yet gotten around to it.”
Conductive Materials Nonconductive materials
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UIC/TRL Atomic Force Microscope • Can use tip either to: – Image, or – Manipulate
Comparison of size ranges for several entities as compared to some nanotechnology devices
1 Nm = 10-9 (one billionth) meter = 10 Å is a magical point on the dimensional scale:
• • • • •
SET - Single-electron transistor GMR - Giant magneto resistive Q-Dots - Quantum dots SEM - Scanning Electron Microscope STM - Scanning Tunneling Microscope From : PRINCIPLES OF NANOTECHNOLOGY G.A. Mansoori, World Sci Pub Co (2005)
Major Advancements
Major Advancements Nanolithography
Discoveries of Fullerene in 1986 & Carbon Nanotube in 1991
Opened the door to the ability to manipulate atoms and molecules on the atomic scale
Xenon atoms on nickel - 1989
Carbon-Based Molecular Building Blocks (nanostructure allotropes of carbon) IBM: Carbon monoxide molecules on copper - 1999 From : PRINCIPLES OF NANOTECHNOLOGY G.A. Mansoori, World Sci Pub Co (2005)
Dip Pen Nanolithography, Piner, R. D.; Zhu, J.; Xu, F.; Hong, S.; Mirkin, C. A. Science, 283, 661-663. 1999
Categories Nanotechnology • Dry Nanotechnology
gy • Wet Nanotechnology = NanoBioTechnology
• Computational Nanotechnology (CNT)
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Active R&D Areas: •
Molecular Building Blocks
Nanobiotechnology: Nanotechnology + Life Sciences
Fullerenes, Carbon Nanotubes, Diamondoids & Derivatives, Dendrimers & other polymers Cyclodextrins, Liposome, Monoclonal Antibody, etc. Metallic & Oxide Nanoparticles (Gold, Silver, ZnO, TiO2, etc.), Quantum Dots/Wells etc.
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Methods & Tools: Computational & Simulations (Molecular Dynamics, ab initio, Monte Carlo, etc.) Nano Property Behavior and Phase Transitions Predictions Positional, Self-Assembly, Self-organization, Protein folding, DNA nanotechnology Dynamic Combinatorial Chemistry, Host-Guest Chemistry (Molecular Design Software) Nano-Processes, Nano-Robotics /Nano-Motions (Molecular Motors), Molecular recognition, Molecular Semiconductors, Nano Lithography
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Major Expected Products / Services Disease diagnostic methods and therapeutic agents (Cancer, Alzheimer’s Disease Nanotechnology , etc.) Nanocircuit boards / Nano-Computers Improved MEMS, introduction of NEMS, Hybrid Materials Nanosensors (Defense, Energy, Environment, Security, etc.)
Therapeutics : A symbolic example
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Source: Bank of America Securities Report
Mansoori Group Research Topics www.uic.edu/~mansoori
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Cancer nanotechnology: a. Melanoma prevention through nanotechnology b. Applications of Azurin as an anti-cancer agent. c. Targeting the Folate Receptor. 2. Silver nanoparticles production and medical applications 3. Onset of Alzheimer’s Alzheimer s disease detection through nanotechnology. 4. Diamomdoids as molecular building block for nanotechnology 5. Applications of supercritical fluid technology for bioseparations 6. Environmental aspects of nanotechnology 7. Molecular based study of condensed matter in small systems
Design, characterization and application of a folate-conjugated gold nanoparticle
Targeting the Folate Receptor, a Novel Cancer Treatment Kenneth S Brandenburg Graduate Student, Bioengineering Department Faculty Advisor: Dr. G. Ali Mansoori, Bioengineering Department
Abstract In this research the author presents studies in the molecular mechanism of Folic Acid – Folate receptor interactions, intermolecular mechanisms of Folic Acid-nanoparticle conjugation and nano-optimization modeling of the most effective conjugation for a targeting strategy. Folate, a salt derivative of Folic Acid, is rapidly gaining acceptance as a targeting ligand for cancer treatments utilizing nanotechnology. In order to optimize a nanoparticle based treatment for cancer, an intense literature review was completed. The review considered: Folate Receptor populations within the human body and abundance, Folate Receptor cycles in endocytosis, Folic Acid — Folate Receptor chemical kinetics, Folate conjugated Nanocarriers, and several proposed nanotechnology based techniques for cancer treatments. Based on the literature review, several areas of Folate – Nanotechnology were identified for future investigation such as Folate Receptor structure imagining, Folate – Conjugate intracellular trafficking, and refinement of nanotechnology based cancer treatments. These future investigations can be accomplished through the use of X-ray crystallography and complex protein folding simulations, Quantum Dots in imaging the intracellular trafficking and delivery of Folate molecules, and further chemical kinetics studies of Folate j g Nano-carriers in vivo. Due to its p promising g conjugated characteristics of non-immunogenicity, specificity for cancer, and easy Nano-carrier conjugation, Folate is a front runner as a targeting system for many cancer treatments and needs to be further explored to validate its use in nanotechnology based cancer therapies.
BioE 396/397 2005-2006
• • • • .
Gold Nanoparticles Conjugated with Folic Acid using Mercaptohexanol as the Linker Journal Nanotechnology Progress International (JONPI), 1: 13-23, 2009. Structural and optical characterization of folate-conjugated gold-nanoparticles Physica E: Low-dimensional Systems and Nanostructures, doi:10.1016/j.physe.2009.10.039. Cancerous Cells Targeting and Destruction Using Folate Conjugated Gold Nanoparticles Dynamic Biochemistry, Process Biotechnology and Molecular Biology, Vol. 4, 2010.(Article in Press) Folate-Conjugated Gold Nanoparticles (Synthesis, characterization and design for cancer cells nanotechnology-based targeting) Int'l J of Nanoscience & Nanotechnology, 2010.(Article in Press)
What is Folate? •Vitamin B-9 •Cofactor for One Carbon Synthesis •Purines and thymidine •Blood Concentration ~ 20nM Folate •Concentration regulated by the Kidneys
Tissue Distribution Tissue
Adult Males (18-24 years)
Infant Females (1-17 months)
Choroid Plexus
Very Strong Positive
Very Strong Positive
Positive
Strong Positive
Positive – Strong Positive
Positive
Folate Receptor Kinetics
Folate Endocytosis •Folate Receptor •38,000 Dalton Protein •Linked in the Hydrophobic region of the phospholipid bilayer •3 Isoforms: Alpha (α), Beta (β), and Gamma (γ) •Does not enter clathrin coated pit pathway
Kidney
Lung
•Units/ml/mg Protein Thyroid Positive •Very Strong Positive: 1000+ •Strong Positive: 100 – 1000 •Positive: 10 – 100 •Weak Positive: 0.1 – 10 Liver Negative •Negative: 0
Positive
•Linear Increase of Association with the number of Folic Acid Molecules Attached •Exponential decrease of Dissociation with the number of Folic Acid Molecules Attached
Negative
Materials Delivered via Folate Material
S l Spleen
N ti Negative Cell Lines
Skin
Positive
Folate Receptor Population Not Done Strong Positive
Monkey Kidney Epithelial cell line (MA104)
Application
2—10
Imaging
Not Done
Fibroblast Less than 0.1 •Healthy tissue: Restricted to the luminal surface [12] Pancreas Weak Positive Positive •Luminal Surface faces away from the blood stream •Prevents the binding of Folate to its receptor in healthy tissues •Cancerous Tissue: Weak The Folate Receptor faces the blood Heart Positive Weak Positive stream Hamster Ovary Chinese Less than 0.1
Ovary
Size (nm)
N ti Negative
Bound Folate (pmol/106 cells)
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Quantum Dots
Future Work •Metallic Folate Receptor structure 0.5—100 Drug Delivery, Thermal • X-Ray diffraction or Protein Folding Simulations Nanoparticles Ablation • Folate Folate--conjugate intracellular trafficking and kinetics • Folate Folate--Conjugate Design • Cleavable bonds for improved drug release and delivery • Other Applications for other diseases
References 1) Iron Oxide (10 nm in diameter) Super paramagnetic particle used to generate the heat necessary to induce hyperthermia. Does not retain magnetism when removed from a magnetic field. 2) Gold (5nm in diameter) Used to prevent aggregation of iron oxide particles. Biomolecules (Folate) can be easily bonded to gold nanoparticles. 3) Folate (Method of Delivery) Cancer cells over express Folate receptors. High solubility in water. High affinity for its receptor 4) Polyethylene Glycol (PEG)
Ovarian Carcinoma (IGROV1)
20 SC: Sub Confluence C: Confluence PC: Post Confluence
Colon Carcinoma (Caco-2)
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1. Doucette MM and Stevens VL. “Folate Receptor Function Is Regulated in Response to Different Cellular Growth Rates in Cultured Mammalian Cells”. Journal of Nutrition. Nutrition. 131 (2001): 28192819-2825 2. Leamon CP and Reddy JA. “Folate“Folate-targeted Chemotherapy.” Advanced Drug Delivery Reviews.. 56 (2004): 1127Reviews 1127-1141 3. Rothberg KG, Ying Y, Kolhouse JF, Kamen BA, and Anderson RGW. “The Glycophospholipid--linked Folate Receptor Internalizes Folate Without Entering the Glycophospholipid Clathrin--coated Pit Endocytic Pathway.” Journal of Cell Biology. Clathrin Biology. 110 (1990): 637637-649 4. Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR, and Kamen BA. “Distribution of the Folate Receptor GP38 in Normal and Malignant Cell Lines and Liposomes/Micelles 30—400 Drug Delivery Tissues.” Cancer Research. Research. 52 (1992): 33963396-3401 5. Hong S, Leroueil PR, Majoros IJ, Orr BG, Baker JR, Banaszak Holl MM. “The Binding Avidity of a NanoparticleNanoparticle-Based Multivalent Targeted Drug Delivery Platform.” Chemistry and Biology. Biology. 14 (2007): 107107-115 6. Nagayasu A, Uchiyama K, and Kiwada H. “The size of liposomes: A Factor which Affects their Targeting Efficiency to Tumors and Therapeutic Activity of Liposomal Antitumor Drugs.” Advanced Drug Delivery Reviews. Reviews. 40 (1999): 7575-87 7. Brandenburg KS, Kent M, Swan D, and Mansoori GA. “Cancer Treatment through Nanotechnology” Senior Design 20052005-2006, Bioengineering 396/397, UIC
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Melanoma prevention through nanotechnology
Acrobat Document
A patent pending.
2. Silver Nanoparticles production and medical applications
Applications of Azurin as an anticancer agent • Azurin: A Novel Anticancer Candidate (Molecular Characteristics, Apoptosis Mechanism and Nanotechnology)
• Biosynthesis of Silver Nanoparticles by Fungus Trichoderma Reesei (A Route for Large-Scale Production of SNP)
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Prospects for Cancer Nanotechnology Treatment by Azurin Dynamic Biochemistry, Process Biotechnology and Molecular Biology, Vol. 4, 2010.(Article in Press)
(Left) TEM micrograph recorded from a drop-coated film of an aqueous solution incubated with Trichoderma reesei and reacted with Ag+ ions for 72 hours. (Right) Selected area of electron diffraction pattern recorded from one of the silver nanoparticles shown in the left Figure. The diffraction rings have been indexed with reference to the fcc silver.
• A patent pending.
3.Alzheimer’s Disease Nanotechnology:
Our team
Early detection of AD through nanotechnology
4. Diamomdoids as molecular building block for nanotechnology Measurement, Simulation and Prediction of Intermolecular Interactions and Structural Characteristics of Organic Nanostructures (Diamondoids and Derivatives)
What we do
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THEORY: Generating & testing the basis sets. Structure optimization. Comparing bond lengths with experiment. Creating and testing potentials for diamondoids & derivatives and pseudopotentials for metal tips. Testing different density functionals (B3LYP, GGA, LSDA & LDA). Testing and comparing results from the ab initio codes ( Molpro, Gaussian 03, etc.). Treating valence electrons exactly.
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EXPERIMENTS: Preparing monolayers of diamondoids. Obtaining images with AFM and/or STM. Preparing samples using different solvents (THF, toluene, etc) with different degrees of concentration levels. Choosing substrates (Si, Mica, etc.). Choosing preparation techniques (drop, spinning, etc.). Force-distance calculations and characterization (through XPS, STM, and AFM). Testing versus THEORY results.
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SIMULATIONS: Simulations to produce self-assemblies for new materials with desired optoelectronic properties as MEMS, NEMS and other micro- and nano-gears and devices. Utilizing the intermolecular potential data produced in the above sections.
Sequential formation of globular amyloid l id aggregates t Our tools 1. Ab initio calculations 2. MD simulation 3. Molecular self-assembly 4. Scanning probe microcopy
Nanotechnology Solutions for Alzheimer's Disease: Journal of Alzheimer's Disease, 13(2): pp. 199-223, 2008.
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5. Applications of supercritical fluid technology for bio systems
Our samples:
Our findings: Sense the hardness
“See” the atoms
Feel the potential
Self-assembly
Our goals:
• In this project we propose to apply supercritical fluid technology for vaporization and ionization of biological aerosols which will not require collection on a substrate or probe.
Supported by the U.S. Army Research Office
The basics of the process
Supercritical fluid screening system to be used in the experimental part of the project
6. Investigating Fate, Transport, Transformation, and Exposure of Engineered Nanomaterials
7. Molecular based study of condensed matter in small systems
Transport, Reactivity, Transformation, and Toxicity of Lactate-Modified Nanoscale Iron Particles In Field Contaminated Soils
Behavior of confined fluids in nanoslit pores: the normal pressure tensor Microfluidics and Nanofluidics, 8(1): pp.97-104,January 2010; DOI: 10.1007/s10404-009-0449-
Structure of nZVI particles
SEM image of nZVI particles
Environmental Applications of Nanotechnology –
BEHAVIOR OF THE CONFINED HARD-SPHERE FLUID WITHIN NANOSLITS: A FUNDAMENTAL-MEASURE DENSITYFUNCTIONAL THEORY STUDY Int'l J of Nanoscience, 7(4-5): pp. 245-253, 2008; DOI: 10.1142/S0219581X08005365. An Analytic Model for Nano Confined Fluids Phase-Transition: Applications for Confined Fluids in Nanotube and Nanoslit J. Comput'l & Theor'l Nanoscience, 3(1):134-141, 2006.
Annual Review of Nano Research, Vol.2, Chapter 2, 2008.
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Some of the expected future products and possibilities resulting from the advances in nanotechnology.
Thank you for your attention Acknowledgements: Collaborators: E.S. de Araujo, L. Assoufid, T.F. George, P. Lopez, A. Nazem, A. Shakeri, Y. Xu, G. Zhang, Financial and technical support: ANL, ARO, MUMS, PEMEX, Surgical Oncology Dep’t, UFPE, UFRPE, UICRRC, UWP
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