In chemotherapy doctors are using a carpet bombing approach to destroy cancer cells: the patient is pumped full of cytotoxic drugs, that go everywhere in the body, with the hope that enough of the drugs reach the cancer cells and target their nuclear DNA to damage it or destroy the cell. Not only do chemotherapeutic techniques have a range of often serious side effects, mainly affecting all the fast-dividing cells of the body, it also has been shown that often less than 1% of the administered drug molecules enter tumor cells and bind to the nuclear DNA. Another complication is drug resistance of cancer cells. This actually is one of the main causes of failure in the treatment of cancer. Dividing cancer cells acquire genetic changes at a high rate, which means that the cells in a tumor that are resistant to a particular drug will survive and multiply. The result is the re-growth of a tumor that is not sensitive to the original drug. Cancer researchers are looking to nanoparticles as a drug carrier capable of localizing and directly releasing drugs into the cell nucleus, thereby circumventing the multidrug-resistance and intracellular drug-resistance mechanisms to effectively deliver drugs to the vicinity of DNA, leading to a high therapeutic efficacy. Scientists now have developed nanoparticles capable of localizing into the nucleus, giving hope to a much more effective cancer chemotherapy that allows to pinpoint individual cells.
The ideal drug carrier may be something out of science fiction. In principle, it is injected into the body and transports itself to the correct target, such as a tumor, and delivers the required dose at this target. This idealized concept was first proposed by Paul Ehrlich at the beginning of the 20th century and was nicknamed the "magic bullet" concept. With the advent of nanotechnology and nanomedicine this dream is rapidly becoming a reality. Nanotechnology has already been applied to drug delivery and cosmetics through the use of liposomal technology, and now nanoparticles and nanotubes present an exciting and more promising alternative.
Cells are the smallest 'brick' in life's building structures. Every living organism is made of cells. Individual cells carry their own DNA and have their own life cycle. Considering that larger organisms, such as humans, are basically huge, organized cell cooperatives, the study of individual live cells is a hugely important scientific task. Among the most significant technical challenges for performing successful live-cell imaging experiments is to maintain the cells in a healthy state and functioning normally on the microscope stage while being illuminated. Especially if scientists want to look into cellular processes that occur in cells in their natural state and that cannot be observed by traditional cytological methods. It is well known that cells move, grow, duplicate, and move from point A to point B. Up to now people studied these mechanical properties with optical microscopes because it is the most common and simple method, very efficient, a very well developed and advanced technology. However, with optical microscopes detection is limited to objects no smaller than the wavelengths of the visible region of light, roughly between 400 and 700 nanometers. Distances or movement smaller than this range cannot be seen with these instruments. Researchers in Kyoto, Japan have applied a near-field optical approach to measure cell mechanics and were able to show intriguing data of nanoscale cell membrane dynamics associated with different phenomena of the cell's life, such as cell cycle and cell death.
Scientists involved in cancer research are showing a lot of interest in carbon nanotubes (CNTs) to be used in basically three cancer-fighting areas. CNTs are being developed as targeted delivery vehicles for anticancer drugs right into cancer cells - think of really, really tiny injection needles. They are also used as the therapeutic agent itself; there is research that shows that CNTs can act as nanoscale bombs that literally blow apart a cancer cell. A third area of application is using CNTs as imaging agents. Particularly single-walled CNTs (SWCNTs) are under active development for various biomedical applications. One of the issues in using CNTs for therapeutic applications is the question of how to get them to the desired place within the organism, say a tumor cell. Another significant problem in applying CNTs for biological applications is that the nanotubes do not stay suspended as discrete nanotubes in aqueous solutions. Coupling the CNT with biomolecules, such as proteins, is a good method for targeting specific sites but has the disadvantage of either reducing protein activity or CNT absorption or both. A novel method demonstrates that it is possible to achieve complete retention of enzymatic activity of adsorbed proteins as well as retention of a substantial fraction of the near-infrared (NIR) absorption of SWCNTs.
In our May 7 spotlight "The potential and the pitfalls of nanomedicine" we took a general look at the potential implications of nanomedicine and addressed some ethical issues that arise as the technology develops. In part two of this article we now take a closer look at emerging nanomedical techniques such as nanosurgery, tissue engineering, nanoparticle-enabled diagnostics, and targeted drug delivery. Again, the ethical issues inherent in these emerging medical technologies need to be considered. There are established principals for ethical assessment of existing, conventional, medical technologies and a new research article examines if and how these principals can be extended to nanomedicine.
In 2005, researchers in the Netherlands developed the concept of a "molecular printboard" (named for its parallels with a computer motherboard) - a monolayer of host molecules on a solid substrate on which guest molecules can be attached with control over position, binding strength, and binding dynamics. Molecules can be positioned on the printboard using supramolecular contact printing and supramolecular dip-pen nanolithography. In this way, nanoscale patterns can be written and erased on the printboard. This technique, which combines top-down fabrication (lithography) with bottom-up methods (self-assembly), has now been applied to proteins. The resulting "protein printboards", allowing the capture and immobilization of proteins with precise control over specificity, strength and orientation, allows the fabrication of protein chips for applications in proteomics. They will play a major role in unraveling the human protein map, just as special chips were instrumental in mapping human DNA.
Most nanobiotechnology research today is focused on human medical applications and, mostly for testing and demonstration purposes, on animals. As nanotechnology is gaining interest with regard to agricultural applications, plant science research focusing on investigation of plant genomics and gene function as well as improvement of crop species has become a nanotechnology frontier. Plant cells differ from animal cells in several aspects, a major one being that they possess a wall surrounding them to provide, among other things, mechanical and structural support. The plant cell wall is generally made up of pollysacharides and cellulose. Cellulose provides a stiff and rigid environment for the cell to live in. Thanks to this wall, viruses have no active way of penetrating plant cells but rely on mechanical wounds or infected seeds for transmission. Researchers are commonly using surface-functionalized silica nanoparticles as nonviral nanocarriers for experimental drug and DNA delivery into animal cells but their use with plants so far was limited due to the cell wall. In a first demonstration of the utilization of porous nanoparticle materials for intracellular controlled release and gene transfer application in plants, researchers have used silica nanoparticles to penetrate the cell wall and deliver a payload into the cell.
For centuries, man has searched for miracle cures to end suffering caused by disease and injury. Many researchers believe nanotechnology may be mankind's first "giant step" toward this goal. Whether these beliefs are based on facts or hope, many corporations and governments are willing to invest a great deal of money to find out what happens when nanotechnology is used for medical applications - the emerging field of nanomedicine. Hundreds of millions, if not billions of dollars have been invested by governments, such as the U.S. National Cancer Institute, and the private sector in nanomedicine research and nanotech-related life sciences ventures. The 2008 budget of the U.S. National Nanotechnology Initiative provides more than $200 million for the National Institutes of Health. The European Union, particularly Germany and the UK, and Japan are also investing heavily in this field. It is difficult to find fault with a technology that promises to cure cancer almost before it starts and prevent the spread of AIDS and other infectious diseases. Scientists around the globe are searching for ways to exploit nanoparticles to improve human health. However, there are toxicological concerns and ethical issues that come with nanomedicine and they have to be addressed alongside the benefits.