19-06-2013, 12:09 PM
Nanomedicine
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ABSTRACT
Nanomedicine is the medical application of nanotechnology.[1] Nanomedicine ranges from the medical applications of nanomaterials, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials. One nanometer is one-millionth of a millimeter.
Nanomedicine research is receiving funding from the US National Institutes of Health. Of note is the funding in 2005 of a five-year plan to set up four nanomedicine centers. In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide.[2]
Overview
The biological and medical research communities have exploited the unique properties of nanomaterials for various applications (e.g., contrast agents for cell imaging and therapeutics for treating cancer). Terms such as biomedical nanotechnology, nanobiotechnology, and nanomedicine are used to describe this hybrid field. Functionalities can be added to nanomaterials by interfacing them with biological molecules or structures. The size of nanomaterials is similar to that of most biological molecules and structures; therefore, nanomaterials can be useful for both in vivo and in vitro biomedical research and applications. Thus far, the integration of nanomaterials with biology has led to the development of diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drug delivery vehicles.
Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future.[3][4] The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging.[5] Neuro-electronic interfaces and other nanoelectronics-based sensors are another active goal of research. Further down the line, the speculative field of molecular nanotechnology believes that cell repair machines could revolutionize medicine and the medical field.
Nanomedicine is a large industry, with nanomedicine sales reaching $6.8 billion in 2004, and with over 200 companies and 38 products worldwide, a minimum of $3.8 billion in nanotechnology R&D is being invested every year.[6] As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.
Medical use of nanomaterials
Two forms of nanomedicine that have already been tested in mice and are awaiting human trials that will be using gold nanoshells to help diagnose and treat cancer, and using liposomes as vaccine adjuvants and as vehicles for drug transport.[7][8] Similarly, drug detoxification is also another application for nanomedicine which has shown promising results in rats.[9] A benefit of using nanoscale for medical technologies is that smaller devices are less invasive and can possibly be implanted inside the body, plus biochemical reaction times are much shorter. These devices are faster and more sensitive than typical drug delivery.[10]
Drug delivery
Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles. The overall drug consumption and side-effects may be lowered significantly by depositing the active agent in the morbid region only and in no higher dose than needed. This highly selective approach would reduce costs and human suffering. An example can be found in dendrimers and nanoporous materials. Another example is to use block co-polymers, which form micelles for drug encapsulation.[11] They could hold small drug molecules transporting them to the desired location. Another vision is based on small electromechanical systems; nanoelectromechanical systems are being investigated for the active release of drugs. Some potentially important applications include cancer treatment with iron nanoparticles or gold shells. A targeted or personalized medicine is intended to reduce the drug consumption and treatment expenses resulting in an overall societal benefit by reducing the costs to the public health system.
Nanomedical approaches to drug delivery center on developing nanoscale particles or molecules to improve drug bioavailability. Bioavailability refers to the presence of drug molecules where they are needed in the body and where they will do the most good. Drug delivery focuses on maximizing bioavailability both at specific places in the body and over a period of time. This can potentially be achieved by molecular targeting by nanoengineered devices.[12][13] It is all about targeting the molecules and delivering drugs with cell precision. More than $65 billion are wasted each year due to poor bioavailability. In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents, images such as ultrasound and MRI have a favorable distribution and improved contrast. The new methods of nanoengineered materials that are being developed might be effective in treating illnesses and diseases such as cancer. What nanoscientists will be able to achieve in the future is beyond current imagination. This might be accomplished by self assembled biocompatible nanodevices that will detect, evaluate, treat and report to the clinical doctor automatically.
Applications and reported research studies
• Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer and non-small- cell lung cancer (NSCLC).,[18] is the nanoparticle albumin bound paclitaxel.
• In a mice study, scientists from Rice University and University of Texas MD Anderson Cancer Center reported enhanced effectiveness and reduced toxicity of an existing treatment for head and neck cancer when using the nanoparticles to deliver the drug. The hydrophilic carbonic clusters functionalized with polyethylene glycol or PEG-HCC are mixed with the chemotherapeutic drug paclitaxel (Taxol) and the epidermal growth factor receptor (EGFR) targeted Cetuximab and injected intravenously. They found the tumors were killed more effectively with radiation and the healthy tissue suffered less toxicity than without the nanotechnology drug delivery. The standard treatment contains Cremophor EL which allows the hydrophobic paclitaxel to be delivered intravenously. Replacing the toxic Cremophor with carbon nanoparticles eliminated its side effect and improved drug targeting which in turn required a lower dose of the toxic paclitaxel.[19]
• Researchers at Case Western Reserve University reported using nanoparticle chain to deliver doxorubicin to breast cancer cells in a mice study. Three magnetic, iron-oxide nanospheres were chemically linked to one doxorubicin-loaded liposome and formed a 100 nm long nanoparticle chain. After the nanochains penetrated the tumor, radiofrequency field was generated that caused the magnetic nanoparticles to vibrate and rupture the liposome, dispersing the drug in its free form throughout the tumor. The result showed that the nano treatment was more effective in halting tumor growth than the standard treatment with doxorubicin. It is also less harmful to healthy cells since only 5% to 10% of the standard dose of doxorubicin were used.[20][21]
• Nanoparticles made of polyethylene glycol (PEG) carrying payload of antibiotics at its core could swift charge thus allowing them to target bacterial infection more precisely inside the body, a group of MIT researchers reported. The nanoparticles, containing a sub-layer of pH sensitive chains of the amino acid histidine, carry a slightly negative charge when circulating in the blood stream, can evade detection and clearing by the immune system. When they encounter an infection site the particles gain a positive charge provoked by the slightly acidic environment at the infection sites, allowing them to bind to the negatively charged bacterial cell walls and release antibiotics at locally high concentration. This nano delivery system can potentially destroy bacteria even it has developed resistance to antibiotics because of the targeted high dose and prolonged release of the drug. Although a lot of work is still needed, the researchers believe that it points to a new direction of using nanotechnology to treat infectious disease.[22][23]
Visualization
Tracking movement can help determine how well drugs are being distributed or how substances are metabolized. It is difficult to track a small group of cells throughout the body, so scientists used to dye the cells. These dyes needed to be excited by light of a certain wavelength in order for them to light up. While different color dyes absorb different frequencies of light, there was a need for as many light sources as cells. A way around this problem is with luminescent tags. These tags are quantum dots attached to proteins that penetrate cell membranes. The dots can be random in size, can be made of bio-inert material, and they demonstrate the nanoscale property that color is size-dependent. As a result, sizes are selected so that the frequency of light used to make a group of quantum dots fluoresce is an even multiple of the frequency required to make another group incandesce. Then both groups can be lit with a single light source.
Neuro-electronic interfaces
Neuro-electronic interfacing is a visionary goal dealing with the construction of nanodevices that will permit computers to be joined and linked to the nervous system. This idea requires the building of a molecular structure that will permit control and detection of nerve impulses by an external computer. The computers will be able to interpret, register, and respond to signals the body gives off when it feels sensations. The demand for such structures is huge because many diseases involve the decay of the nervous system (ALS and multiple sclerosis). Also, many injuries and accidents may impair the nervous system resulting in dysfunctional systems and paraplegia. If computers could control the nervous system through neuro-electronic interface, problems that impair the system could be controlled so that effects of diseases and injuries could be overcome. Two considerations must be made when selecting the power source for such applications. They are refuelable and nonrefuelable strategies. A refuelable strategy implies energy is refilled continuously or periodically with external sonic, chemical, tethered, magnetic, or electrical sources. A nonrefuelable strategy implies that all power is drawn from internal energy storage which would stop when all energy is drained.
Medical applications of molecular nanotechnology
Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale. Molecular nanotechnology is highly theoretical, seeking to anticipate what inventions nanotechnology might yield and to propose an agenda for future inquiry. The proposed elements of molecular nanotechnology, such as molecular assemblers and nanorobots are far beyond current capabilities.
Nanorobots
The somewhat speculative claims about the possibility of using nanorobots[43] in medicine, advocates say, would totally change the world of medicine once it is realized. Nanomedicine[1][42] would make use of these nanorobots (e.g., Computational Genes), introduced into the body, to repair or detect damages and infections. According to Robert Freitas of the Institute for Molecular Manufacturing, a typical blood borne medical nanorobot would be between 0.5-3 micrometres in size, because that is the maximum size possible due to capillary passage requirement. Carbon could be the primary element used to build these nanorobots due to the inherent strength and other characteristics of some forms of carbon (diamond/fullerene composites), and nanorobots would be fabricated in desktop nanofactories [44] specialized for this purpose.
Nanonephrology
Nanonephrology is a branch of nanomedicine and nanotechnology that seeks to use nano-materials and nano-devices for the diagnosis, therapy, and management of renal diseases. It includes the following goals:
1. the study of kidney protein structures at the atomic level
2. nano-imaging approaches to study cellular processes in kidney cells
3. nano medical treatments that utilize nanoparticles to treat various kidney diseases
Advances in Nanonephrology are expected to be based on discoveries in the above areas that can provide nano-scale information on the cellular molecular machinery involved in normal kidney processes and in pathological states. By understanding the physical and chemical properties of proteins and other macromolecules at the atomic level in various cells in the kidney, novel therapeutic approaches can be designed to combat major renal diseases. The nano-scale artificial kidney is a goal that many physicians dream of. Nano-scale engineering advances will permit programmable and controllable nano-scale robots to execute curative and reconstructive procedures in the human kidney at the cellular and molecular levels. Designing nanostructures compatible with the kidney cells and that can safely operate in vivo is also a future goal. The ability to direct events in a controlled fashion at the cellular nano-level has the potential of significantly improving the lives of patients with kidney diseases.