Nanobiotechnology
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Nanobiotechnology involves the manipulation of matter at the nanoscale (1-100 nanometers) for applications in biology. Key developments include the atomic force microscope in 1980, which enabled imaging at the atomic level. Nanoparticles such as quantum dots have been used for in vivo cell imaging due to their strong fluorescent signals. Nanodevices have the potential to improve cancer detection and diagnosis by entering cells to determine which are cancerous. They may also preserve patient samples and make tests faster. Challenges include assessing the toxicity and biocompatibility of nanomaterials. Overall, nanobiotechnology could lead to new biomaterials and analytical tools with applications in medicine such as targeted drug delivery and disease diagnosis and treatment.
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Nanobiotechnology
- 1. NANOBIOTECHNOLOGY • • • • • Haris Saddique Mphil Scholar Department of biotechnology University of Malakand Kpk Pakistan
- 3. • Richard P. Feynman (nobelist,1965) is credited with the birth of nanotechnology. 1959 Lecture title “There is plenty of room at the bottom” • Challenged the scientific community : 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.”
- 4. Nanotechnology Creation of useful materials, devices, and systems through the manipulation of matter on nanometer scale. Generally nanotechnology deals with structures sized between 1 to 100 nanometer. Involves developing materials, devices within that size, which can be used for analysis and measurement on a molecular scale Interdisciplinary area : Biology, Physics, Chemistry, Material science, Electronics, Chemical Engineering, Information technology
- 5. Nanotechnology Plays Different Role Normal scale Nanoscale
- 6. Nano-Biotechnology Integration of nano-sized/structured materials, nano-scale analytical tools, and nano-devices into biological sciences for development of new biomaterials and analytical toolkits as well as for understanding life science Typical characteristics of Biological events/materials - Self assembly - Highly efficient - Very specific : extremely precise
- 7. Analytical methods and Nano-sized materials Analytical tools : Atomic force microscopy(AFM), Electron microscopy (EM) Scanning Tunneling Microscope (STM) Magnetic resonance imaging(MRI) Nano-sized materials 3 Major Groups of nano particles – Natural Nanoparticles Volcanic Ash Magnetotactic bacteria Mineral composites – Industrial Nanoparticles Ni , Pb nanoparticles – Engineered Nanoparticle Manufactured by man- synthesis, processing of Nanomaterial ( Nano tubes. Quantum Dots etc.,)
- 8. Nano-Bio Nano-Bio Convergence Convergence Bio-inspired device and system Bio-Technology Nano-Technol Molecular Imaging Molecular Switch DNA barcode Biochip / Biosensor Nanotherapy / Delivery Bionanmachine / Nano-Roboto-
- 9. Applications and Perspectives of Nanobiotechnology Development of tools and methods - More sensitive More specific Multiplexed More efficient and economic Implementation Diagnosis and treatment of diseases - Rapid and sensitive detection (Biomarkers, Imaging) - Targeted delivery of therapeutics Drug development - Understanding of life science
- 10. Examples Nano-Biodevices Nano-Biosensors Imaging with nanoparticles Analysis of a single molecule/ a single cell
- 11. Issues to be considered Synthesis or selection of nano-sized/ structured materials Functionalization with biomolecules or for biocompatibility Integration with devices and/or analytical tools Assessment : Reproducibility, Toxicity Implementation
- 12. The size of Things
- 13. NanoBiotech was initiated by the development of AFM that enables imaging at atomic level in 1980
- 14. AFM (Atomic Force Microscope) One of the foremost tools for imaging, measuring, and manipulating matters at the nanoscale. A cantilever with a sharp tip (probe) at its end that is used to scan the specimen surface When the top is brought into a close proximity of a sample surface, force between the tip and sample leads to a deflection of the cantilever according to Hooke’s law Deflection is measured using a laser spot reflected from the top surface of the cantilever into an array of photodiode
- 15. VEECO TESPA® Tip length : 10 µm Radius : 15~20 nm VEECO TESPA-HAR® Tip length :10 µm (last 2 µm 7:1) Radius : 4~10 nm NANOWORLD SuperSharpSilicon® Tip length :10 µm Radius : 2 nm
- 16. Example showing the resolution of protein structure by AFM Image of ATP synthase composed of 14subunits
- 17. MRI and Cell Tracking Enhanced MR Imaging of a Mouse Brain Tumor Using Gadolinium-containing Nanoparticles Pre- cont rast Postcontrast 5 hr Postcontrast
- 18. Semiconductor Nanocrystals Quantum Dots - Properties and Biological Applications
- 19. Synthesis of CdSe/ZnS (Core/Shell) QDs Step 1 CdO + Se CdSe Solvent : TOPO, HAD, TOP Surfactant : TDPA, dioctylamine Step 2 CdSe/ZnS 5.5 nm (red) ZnS ZnEt2 + S(TMS)2 CdSe Growth temperature 140 ℃ (green) 200 ℃ (red) Ar Thermocouple Se solution CdO solution 320 ℃ 20 nm Bawendi et al. J. Am. Chem. Soc. (1994)
- 20. YY Y In Vivo Cell Imaging YY YY QD + Organelle Y QD-Antibody conjugates YY QD YY YY Y Antigen ▲ 3T3 cell nucleus stained with red QDs and microtubules with green QDs Organelle -- Multiple Color Imaging Multiple Color Imaging -- Stronger Signals Stronger Signals Wu et al. Nature Biotech. 2003 21 41 Y
- 21. In Vivo Cell Imaging Live Cell Imaging Quantum Dot Injection ▶ Red Quantum Dot locating a tumor in a live mouse Cell Motility Imaging 10um ◀ Green QD filled vesicles move toward to nucleus (yellow arrow) in breast tumor cell Alivisatos et al., Adv. Mater., 2002 14 882
- 22. What Is NanoBiotechnology? Water Nanodevices molecule Nanopores Dendrimers Nanotubes Quantum dots Nanoshells White blood cell A period Tennis ball
- 24. Nanodevices Are Small Enough to Enter Cells Cell Nanodevices Nanodevices Water molecule White blood cell
- 25. Nanodevices Can Improve Cancer Detection and Diagnosis NanoBiotechnology Imaging Physical Exam, Symptoms
- 26. Nanodevices Can Improve Sensitivity Nanodevices could potentially enter cells Precancerous cells Normal cells and determine which cells are cancerous or precancerous. Precancerous cells Normal cells
- 27. Nanodevices Can Preserve Patients’ Samples Traditional Tests Cells from patient Cells altered Active state lost Nanotechnology Tests Cells from patient Cells preserved Active state preserved Additional tests
- 28. Nanodevices Can Make Cancer Tests Faster and More Efficient Patient A Patient B
- 29. Cantilevers Can Make Cancer Tests Faster and More Efficient Cancer cell Antibodies with proteins Antibodies Bent cantilever Water molecule White blood cell Nanodevices Cantilevers
- 31. Quantum Dots Ultraviolet light off Quantum dot bead Water molecule Ultraviolet light on Quantum dots Nanodevices Quantum dots Quantum dots emit light White blood cell
- 32. Quantum Dots Can Find Cancer Signatures Quantum dot beads Cancer cells Healthy cells Cancer cells Quantum dot beads Healthy cells
- 33. Improving Cancer Treatment Traditional Treatment Drugs Nanotechnology Treatment Toxins Nanodevices Cancer cells Cancer cells Noncancerous cells Dead cancer cells Dead noncancerous cells Toxins Noncancerous cells Dead cancer cells Intact noncancerous cells
- 34. Nanoshells Near-infrared light off Nanoshell Near-infrared light on Gold Nanoshell absorbs heat Water molecule Nanodevices Nanoshells White blood cell
- 35. Nanoshells as Cancer Therapy Nanoshells Nanoshells Cancer cells Cancer cells Healthy cells Healthy cells Near-infrared light Dead cancer cells Intact healthy cells
- 36. Nanodevices as a Link Between Detection, Diagnosis, and Treatment Traditional Cancer Treatment NanoBiotechnology Cancer Treatment Cancer cell Cancer cell Nanodevice Drug Imaging Reporting Detection Targeting
- 37. Dendrimers Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units - Not more that 15 nm in size, Mol. Wt very high - Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers) Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm • Dendrimers consist of series of chemical shells built on a small core molecule - Surface may consist of acids or amines ⇒ means to attach functional groups ⇒ control/modify properties - .
- 39. Poly (amido amine) Dendrimers ● Characteristics Monodisperse macromolecule Globular (Spherical) smooth surface Similar molecular size to biomolecules ● Applications Vehicles for delivery of genes and drugs 4.5 nm G4 Poly(amidoamine) Dendrimer Medical applications (MRI contrast enhancer) Molecular carriers for chemical catalysts
- 40. Dendrimers as Cancer Therapy Manipulate dendrimers to release their contents only in the presence of certain trigger (molecules or light) caged molecules Therapeutic agent Cancer detector Cell death monitor Reporter Water molecule Nanodevices Dendrimer White blood cell
- 41. Nanotubes CNT is a tubular form of carbon with diameter as small as 1 nm 1. 2. 3. Nanotubes offer some advantages relative to nanoparticles by the following aspects: Larger inner volumes – can be filled with chemical or biological species. Open mouths of nanotubes make the inner surface accessible. Distinct inner and outer surface can be modified separately.
- 42. Functional AFM tips 2+ 2+ 3+ 3+ e DNA sequencing Bio-sensors
- 43. Cell interactions by nano particles
- 44. BENEFITS TO MANKIND • Early detection of viruses by nano sensors (Used in bio-logical wars - Detection of anthrax) • Break through in cancer cell targeting, monitoring & therapy • Control of AIDS • Targeted drug delivery • Clean environment • Clinical Application aspects in respective fields (Ophthalmology, Radiology & Imaging Services, Orthopedics, Clinical Embryology, Medical Genetics & Regenerative Medicine)
- 45. Future goals of nanobiotech Nanobiotechnology may be able to create many new materials and devices with a vast range of applications, such as in medicine, biomaterials and energy production. Nanobiotechnology raises many of the same issues as with any introduction of new technology, including concerns about the toxicity and environmental impact of nanomaterials, and their potential effects on global economics.
Notes de l'éditeur
- Much of today’s nanoscale research is designed to reach a better understanding of how matter behaves on this small scale. The factors that govern larger systems do not necessarily apply at the nanoscale. Because nanomaterials have large surface areas relative to their volumes, phenomena like friction and sticking are more important than they are in larger systems.
- TESPA : TappingMode Etched Silicon Probes (Aluminiun-coated) HAR : High Aspect Ratio
- A nanometer is a billionth of a meter. It’s difficult to imagine anything so small, but think of something only 1/80,000 the width of a human hair. Ten hydrogen atoms could be laid side-by-side in a single nanometer. Nanotechnology is the creation of useful materials, devices, and systems through the manipulation of matter on this miniscule scale. The emerging field of nanotechnology involves scientists from many different disciplines, including physicists, chemists, engineers, and biologists. There are many interesting nanodevices being developed that have a potential to improve cancer detection, diagnosis, and treatment.
- Most animal cells are 10,000 to 20,000 nanometers in diameter. This means that nanoscale devices (less than 100 nanometers) can enter cells and the organelles inside them to interact with DNA and proteins. Tools developed through nanotechnology may be able to detect disease in a very small amount of cells or tissue. They may also be able to enter and monitor cells within a living body.
- Detection of cancer at early stages is a critical step in improving cancer treatment. Currently, detection and diagnosis of cancer usually depend on changes in cells and tissues that are detected by a doctor’s physical touch or imaging expertise. Instead, scientists would like to make it possible to detect the earliest molecular changes, long before a physical exam or imaging technology is effective. To do this, they need a new set of tools.
- In order to successfully detect cancer at its earliest stages, scientists must be able to detect molecular changes even when they occur only in a small percentage of cells. This means the necessary tools must be extremely sensitive. The potential for nanostructures to enter and analyze single cells suggests they could meet this need.
- Many nanotechnology tools will make it possible for clinicians to run tests without physically altering the cells or tissue they take from a patient. This is important because the samples clinicians use to screen for cancer are often in limited supply. It is also important because it can capture and preserve cells in their active state. Scientists would like to perform tests without altering cells, so the cells can be used again if further tests are needed.
- nanotechnology will allow the tools for many different tests to be situated together on the same small device. Researchers hope that nanotechnology will allow them to run many diagnostic tests simultaneously.
- One nanodevice that can improve cancer detection and diagnosis is the cantilever. These tiny levers, which are anchored at one end, can be engineered to bind to molecules that represent some of the changes associated with cancer. They may bind to altered DNA sequences or proteins that are present in certain types of cancer. When these molecules bind to the cantilevers, surface tension changes, causing the cantilevers to bend. By monitoring the bending of the cantilevers, scientists can tell whether molecules are present. Scientists hope this property will prove effective when cancer-associated molecules are present--even in very low concentrations--making cantilevers a potential tool for detecting cancer in its early stages.
- Another interesting nanodevice is the nanopore. Improved methods of reading the genetic code will help researchers detect errors in genes that may contribute to cancer. Scientists believe nanopores, tiny holes that allow DNA to pass through one strand at a time, will make DNA sequencing more efficient. As DNA passes through a nanopore, scientists can monitor the shape and electrical properties of each base, or letter, on the strand. Because these properties are unique for each of the four bases that make up the genetic code, scientists can use the passage of DNA through a nanopore to decipher the encoded information, including errors in the code known to be associated with cancer.
- Another minuscule molecule that will be used to detect cancer is a quantum dot. Quantum dots are tiny crystals that glow when they are stimulated by ultraviolet light. The wavelength, or color, of the light depends on the size of the crystal. Latex beads filled with these crystals can be designed to bind to specific DNA sequences. By combining different sized quantum dots within a single bead, scientists can create probes that release distinct colors and intensities of light. When the crystals are stimulated by UV light, each bead emits light that serves as a sort of spectral bar code, identifying a particular region of DNA.
- To detect cancer, scientists can design quantum dots that bind to sequences of DNA that are associated with the disease. When the quantum dots are stimulated with light, they emit their unique bar codes, or labels, making the critical, cancer-associated DNA sequences visible. The diversity of quantum dots will allow scientists to create many unique labels, which can identify numerous regions of DNA simultaneously. This will be important in the detection of cancer, which results from the accumulation of many different changes within a cell. Another advantage of quantum dots is that they can be used in the body, eliminating the need for biopsy.
- Nanotechnology may also be useful for developing ways to eradicate cancer cells without harming healthy, neighboring cells. Scientists hope to use nanotechnology to create therapeutic agents that target specific cells and deliver their toxin in a controlled, time-released manner.
- Nanoshells are miniscule beads coated with gold. By manipulating the thickness of the layers making up the nanoshells, scientists can design these beads to absorb specific wavelengths of light. The most useful nanoshells are those that absorb near-infrared light, which can easily penetrate several centimeters of human tissue. The absorption of light by the nanoshells creates an intense heat that is lethal to cells.
- Researchers can already link nanoshells to antibodies that recognize cancer cells. Scientists envision letting these nanoshells seek out their cancerous targets, then applying near-infrared light. In laboratory cultures, the heat generated by the light-absorbing nanoshells has successfully killed tumor cells while leaving neighboring cells intact.
- Researchers aim eventually to create nanodevices that do much more than deliver treatment. The goal is to create a single nanodevice that will do many things: assist in imaging inside the body, recognize precancerous or cancerous cells, release a drug that targets only those cells, and report back on the effectiveness of the treatment.
- Research is being done on a number of nanoparticles created to facilitate drug delivery. One such molecule with potential to link treatment with detection and diagnosis is known as a dendrimer. Dendrimers are man-made molecules about the size of an average protein, and have a branching shape. This shape gives them vast amounts of surface area to which scientists can attach therapeutic agents or other biologically active molecules. Researchers aim eventually to create nanodevices that do much more than deliver treatment.
- A single dendrimer can carry a molecule that recognizes cancer cells, a therapeutic agent to kill those cells, and a molecule that recognizes the signals of cell death. Researchers hope to manipulate dendrimers to release their contents only in the presence of certain trigger molecules associated with cancer. Following drug release, the dendrimers may also report back whether they are successfully killing their targets.