Nanomedicine and Disease

Nanoparticles are taking over the world of biomedicine. Image ©Chris Ewels (www.ewels.info)..

Nanotechnology refers to the use man-made of nano-sized (typically 1-100 billionths of a meter) particles for industrial or medical applications suited to their unique properties. Physical properties of known elements and materials can change as their surface to area ratio is dramatically increased, i.e. when nanoscale sizes are achieved. These changes do not take place when going from macro to micro scale.

Changes in physical properties such as colloidal properties, solubility and catalytic capacity have been found very useful in areas of biotechnology, such as bioremediation and drug delivery.

The very different properties of the different types of nanoparticles have resulted in novel applications. For example, compounds known to be generally inert materials, may become catalysts. The extremely small size of nanoparticles allows them to penetrate cells and interact with cellular molecules. Nanoparticles often also have unique electrical properties and make excellent semiconductors and imaging agents. Because of these qualities, the science of nanotechnology has taken off in recent years, with testing and documentation of a broad spectrum of novel uses for nanoparticles, particularly in nanomedicine.

The development of nanotechnologies for nanomedical applications has become a priority of the National Institutes of Health (NIH).

Between 2004 and 2006, the NIH established a network of eight Nanomedicine Development Centers, as part of the NIH Nanomedicine Roadmap Initiative. In 2005, The National Cancer Institute (NCI) committed 144.3 million over 5 years for its “Alliance for Nanotechnology in Cancer” program which funds seven Centres of Excellence for Cancer Nanotechnology (Kim, 2007).

The funding supports various research projects in areas of diagnostics, devices, biosensors, microfluidics and therapeutics.

Among the long term objectives of the NIH initiative are goals such as being able to use nanoparticles to seek out cancer cells before tumors grow, remove and/ or replace “broken” parts of cells or cell mechanisms with miniature, molecular-sized biological “machines”, and use similar “machines” as pumps or robots to deliver medicines when and where needed within the body. All of these ideas are feasible based on present technology. However, we don’t know enough about the physical properties of intracellular structures and interactions between cells and nanoparticles, to currently reach all of these objectives. The primary goal of the NIH is to add to current knowledge of these interactions and cellular mechanisms, such that precisely-built nanoparticles can be integrated without adverse side-effects.

Many different types of nanoparticles currently being studied for applications in nanomedicine.

They can be carbon-based skeletal-type structures, such as the fullerenes, or micelle-like, lipid-based liposomes, which are already in use for numerous applications in drug delivery and the cosmetic industry. Colloids, typically liposome nanoparticles, selected for their solubility and suspension properties are used in cosmetics, creams, protective coatings and stain-resistant clothing. Other examples of carbon-based nanoparticles are chitosan and alginate-based nanoparticles described in the literature for oral delivery of proteins, and various polymers under study for insulin delivery.

Additional nanoparticles can be made from metals and other inorganic materials, such as phosphates. Nanoparticle contrast agents are compounds that enhance MRI and ultrasound results in biomedical applications of in vivo imaging. These particles typically contain metals whose properties are dramatically altered at the nano-scale. Gold “nanoshells” are useful in the fight against cancer, particularly soft-tissue tumors, because of their ability to absorb radiation at certain wavelengths. Once the nanoshells enter tumor cells and radiation treatment is applied, they absorb the energy and heat up enough to kill the cancer cells. Positively-charged silver nanoparticles adsorb onto single-stranded DNA and are used for its detection. Many other tools and devices for in vivo imaging (fluorescence detection systems), and to improve contrast in ultrasound and MRI images, are being developed.

There are numerous examples of disease-fighting strategies in the literature, using nanoparticles. Often, particularly in the case of cancer therapies, drug delivery properties are combined with imaging technologies, so that cancer cells can be visually located while undergoing treatment. The predominant strategy is to target specific cells by linking antigens or other biosensors (e.g. RNA strands) to the surface of the nanoparticles that detect specialized properties of the cell walls. Once the target cell has been identified, the nanoparticles will adhere to the cell surface, or enter the cell, via a specially designed mechanism, and deliver its payload.

One the drug is delivered, if the nanoparticle is also an imaging agent, doctors can follow its progress and the distribution of the cancer cell is known. Such specific targeting and detection will aid in treating late-phase metastasized cancers and hard-to-reach tumors and give indications of the spread of those and other diseases. It also prolongs the life of certain drugs that have been found to last longer inside a nanoparticle than when the tumor was directly injected, since often drugs that have been injected into a tumor diffuse away before effectively killing the tumor cells.

A significant development in the treatment of cancer was the pairing of siRNA (small interfering RNA) treatments with nanoparticle delivery. In 1999, siRNA was first described as a novel means of inhibiting protein expression in cells. However, the RNA strands were often destroyed by cellular mechanisms before reaching their targets. Nanoparticles provide the protection and delivery mechanisms siRNA molecules need to reach target tissues.

Several companies have already entered clinical trials of nanoparticles-delivered siRNA therapies (Alper 2006).

Molecular self-assembly is the phenomenon through which molecules assemble spontaneously into defined, stable formations based on atomic interactions such as hydrogen bonding, hydrophobic and van der Waals forces. “Bottom-up” construction of nanoparticles takes advantage of molecular self-assembly to build specific structures based on our understanding of these spontaneous formations. One application of this is to use the specificity of Watson-Crick DNA base pairing to build nucleic acids of defined structures with particular uses. In another novel application of molecular self-assembly, under development in Switzerland, pore proteins are introduced into nanoparticles during polymer assembly. The pores are incorporated into the surface matrix, and their opening and closing allow drug delivery specific to certain environmental conditions (in this case pH changes) in the cell (Broz et al.

2006). Pores often open or close as they react to pH, temperature or other environmental factors. Use of similar pores in nanoparticles allows specific delivery or biosensing under specific cellular conditions, for example, insulin delivery when blood sugar levels indicate a need.

Following payload delivery, it is often desirable for the nanoparticles to somehow be removed or metabolized, ideally without any toxic side effects.

Indeed, the advantages to using nanoparticles are that toxic side effects of traditional radiation and chemotherapies can be avoided, by treating only the tumor, or unhealthy, cells and not damaging nearby healthy tissue. Some nanoparticles are expected to be relatively safe because of their propensity to dissolve once inside cells, and some consist of materials that are already in use in biomedicine, such as nanoparticles made from the same polymers as are used for sutures (Bullis, 2006). Whatever the approach, the benefits of nanoparticle delivery are enormous and include improved bioavailability of drugs by targeting specific organs, tissues or tumors, thereby providing the highest dose of drug directly where it is needed, and reducing waste and costs due to breakdown prior to a drug meeting its target.

Nanomedicine is a relatively new area of biotechnology, but the possibilities for new therapies and surgeries to treat illnesses and diseases such as cancer, seem endless. The concept of nanorobots and cell repair machines is also viable and may some day be as commonplace as taking an asprin is today.

Sources:

Kim, 2007. Nanotechnology platforms and physiological challenges for cancer therapeutics. In Press, doi.org/10.1016/j.nano.2006.12.002.

Alper, 2006, Nanoparticles and siRNA – Partners on the pathway to new cancer therapies. NCI Alliance for Nanotechnology in Cancer. http://nano.cancer.gov/news_center/monthly_feature_2006_august.asp.

Broz et al., 2006. Toward intelligent nanosize bioreactors: A pH-switchable, channel-equipped, functional polymer nanocontainer. Nano Letters 6(10): 2349-2353.

Bullis, 2006. Single-Shot Chemo. Technology Review. http://www.technologyreview.com/read_article.aspx?ch=specialsections&sc=emergingtech&id=16469.

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