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Nanomedicine

D.Blicq dblicq@rrc.mb.ca         04-01-2010           DIRECTORY I BIO I NOTICE BOARD

"Nanomedicine" is used to describe medical technologies that occur at the molecular (or nano) levels. "Nanaomedicine" is also used to describe a range of activities, including diagnostics, therapeutics,  preventative measures and other medical interventions which impact upon human health.

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The fundamental significance of microscopic medicine is that the nanometer scale represents the physical range occupied by living cells in which they normally function - nanomedicine seeks to identify, diagnose and treat medical conditions at the cellular level itself.

With the advent of nanodevices capable of operating at the cellular level an entirely new world of medicine is being developed with highly significant implications.  Over time, as effective nano-techniques are developed and implemented there will be remarkable benefits.

General benefits include:

  1. Enhanced Diagnostics - diagnosis and repair of conditions such as genetic abnormalities before the physical expression of the disease occurs

  2. Sensitivity and Resolution - the ability to resolve cellular-level conditions in order to commence successful therapies will be greatly enhanced. Small, even molecular-level conditions can be observed and assessed at the cellular level, long before the disease condition affects the whole organism.

  3. Automation - self-directing nano-machines will be capable of seeking out diseased cells and damaged genetic information, initiating repairs and enhancing health at the cellular level.

  4. Artificial Immunology - pre-programmed micromachines could be set to track down and eliminate specific disease conditions such as cancer or cardiac dysfunction. This automation could operate as an artificial immune system with micromachines seeking and eliminating problems long before any noticeable onset of disease.

  5. Nano-surgery - surgical procedures conducted at the molecular level will have a degree of accuracy and level of non-invasiveness  never before imagined.

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Developing Medical Applications include:

  1. Particle Technologies - development of metal nanoparticles, specialized polymer-based  nanoparticles, as well as fat / lipid nanosystems.
  2. Molecular chemistry - nanochemistry techniques to prepare and create nanoparticles for specialized cellular and /or molecular tasks.
  3. Cancer and Oncogenics - development of new diagnostic tools and techniques for diagnosis,  imaging, and therapeutic purposes.
  4. Drug Delivery Systems - molecular-level delivery of pharmaceuticals and other therapeutic agents targeted at the molecular or genetic levels.
  5. Molecular Manipulation - creation of nanoparticles which are magnetic (or with other applicable characteristics) that can be manipulated via electromagnetic fields. "Tagging" of specified molecules, cells and tissues will allow for exceptionally accurate diagnosis and treatment of tumors and other conditions.
  6. Clinical Applications - development of practical applications of nanomedicine to clinical practice for diagnostic and therapeutic purposes.

Case Study - "Nanocircles" as Gene Therapy

Researchers at Stanford University are developing genetic therapies at the molecular level. The technique involves creation of a "nanocircle" - a small, artificial, plasmid-like ring of DNA which is designed to enter a cell and shut down the activity of a disease-causing gene. The real importance of the work is that it highlights both the preventative and therapeutic capabilities of nanomedicine.

 

Many microorganisms have a small amount of additional genetic information stored in small circles / rings of DNA called "plasmids".  Molecular biologists have long used these small DNA rings to transfer genetic information into appropriate host organisms (i.e. genetic engineering). What is new however, is the idea of artificially creating a plasmid (or in this case nanocircle) that serves to enter a cell and genetically repair a disease condition. Consider the implication: the ability to design and delivery a "genetic patch" for a broad spectrum of medical conditions.

The technique employed by Stanford researchers is termed "RCA - Rolling Circle Amplification". The key requirement was the development of an effective nanocircle - a synthetic plasmid which would integrate with the host E.Coli DNA and produce enough enzymes / ribozymes when expressed to permanently alter the cell's DNA.

The work shows significant promise: the target gene was blocked with a >90% success rate.  Interestingly, the future  potential may outweigh the immediate success - the ability to have nanomedical devices enter cells and target their own resources to correct genetic or somatic abnormalities could forever alter the practice of medicine.  Further work will examine shutting down a gene in a pathogenic microorganism / bacteria to see if there is a genetic equivalent of antibiotics.

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Nanofluidics - the use of nanotools to measure, count and sort biomolecules

Researchers at Cornell University have constructed microscopic silicon devices to sort, count and measure biomolecules in what they have termed "nanofluidics".  This technique accomplishes all of the information gathering of contemporary electrophoretic methods, but also involves the use of specifically-constructed nano-structures.  The technique separates biomolecules in three ways:

  1. Aqueous Gyration - building a structure with small holes that forces aqueous genetic materials to separate on the basis of size.
  2. Physical Length - a series of nano-scale pillar structures separates biomolecules on the basis of length using pulses of electrical current.
  3. Lateral Diffusion - separation using "Brownian Ratchets" which allow separation on the basis of size.

Separation of DNA (and other key biomolecules) seems to consistently involve building molecular  obstacles or tunnels to variably impede the progress of different molecules. Future research will examine the concept of molecular separations for other biomolecules, allowing researchers and therapists to select individual types of molecules from a complex mixture.

Case Study: Nano-scale Fibre-Optic Pressure Sensor

Researchers in Japan have developed a microscopic fibre optic device for measuring blood pressure in blood vessels during catherization procedures.  This nano-scale device (about 125μm ) consists of a fibre optic thread with a microscopic diaphragm on the end which responds to exceptionally small localized variations in blood pressure. Unlike other technologies, this type of micro-mechanical sensor is not sensitive to interference by electromagnetic radiation.

This type of nano-device allows a level of accuracy and precision in measurements which will support effectiveness of surgical procedures and minimize blood loss during surgery.

NanoDiagnostics

Not that long ago all diagnostics of infectious disease were based on biotyping - examination of physical, growth related characteristics to identify infectious organisms. This typically includes petri plate counts and other traditional diagnostic methods.  With development of molecular biology, extensive molecular diagnostic techniques have been established and put into practice: PCR,  RFLP analysis, LCR, etc. All of these techniques employ natural enzymes to conduct absolutely precise molecular-level work to identify and characterize infectious agents.  This significant enhancement has had a profound impact on strategies for studying, identifying and treating infectious agents.

Nanotechnology is now set to provide another profound level of enhancement to medical diagnostics. One of the fundamental ways to identify biological materials is to "tag" or otherwise identify the material with something that's easy to locate: a fluorescent dye, a specific antibody, a magnetic particle, etc.

Examples include:

  1. Magnetic immunoassays - combinations of magnetic micro-beads and antibodies for specific substrates / materials
  2. Gold-linked DNA particles used to rapidly locate key identifying sequences from pathogenic organisms
  3. Nanodot Coding - Conversion of DNA sequence information into computer-readable nanodots
  4. Tissue Differentiation - Induced differential reflectivity to identify diseased tissues and target organisms
  5. Electronic Signatures - molecular level characterization based on nano-identification of key consensus sequences of DNA in a cell, tissue, or individual.

NanoScaffolding

NanoScaffolding is an extremely promising development is tissue re-growth and regeneration.  The technique (initially investigated by a group in Sheffield England) is also being studied by the U.S. military among others) and involves. The method employs nano-scaffolds: microscopic polymer structures upon which cells can grow, divide and re-create tissues and other more complex structures.

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The nanoscaffold serves as a guide for cells to adhere to as they replicate, rapidly growing through and over the porous scaffold structure.  The U.S. military has reported success in the re-growth of fingertips, bladders and other organs, and there is tremendous promise for future techniques to repair damaged or even absent human organs.

NanoTherapy

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A wide range of activities may be can be described as "nanotherapeutics." Examples include:

  1. Nanoparticles - NanoDots - gold (and other materials) are used to tag diseased or target tissues for selective and / or discretionary treatment
  2. Phototherapeutics - the use of microlaser energy to destroy damaged tissues tagged with nanoparticles (gold-antibody conjugates)
  3. Gene Therapy - replacement of diseased DNA sequences through molecular-level repair. May include replacement or elimination of damaged sequences.  Gene therapy has long been a target of molecular biologists who may now have access to the tools which support gene replacement.
  4. Drug Delivery - drug development will benefit enormously from nanomedicine - from initial formulation science to delivery and clinical applications. Outcomes will likely include effective enhancements in drug solubility, reduced dosages of pharmaceutics applied more specifically to target tissues. Other applications will include microscopic controlled-release devices.

Modern medicine will begin to see nanotechnology influencing diagnostics, therapeutics and research activities over the next decade.

Nanomedicine

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