Sunday, December 19, 2004

Biological implications of medicinal nanotechnology

Today’s Physicians are being constantly bombarded by the latest technology. But, where is all this stuff really coming from. The thrust is the quest to climb inside our bodies and repair the problem as easy as it is to simply stretch out our hands and straighten the pictures on out walls..... Take VivaGel as an example. VivaGel is being developed as a topical microbicide that has the potential to prevent the transmission of HIV and other STDs when applied to the vagina prior to sexual intercourse. In earlier studies performed in monkeys, VivaGel was found to be highly effective in preventing HIV transmission. VivaGel is the first drug product based upon nanoscale molecules called dendrimers to enter human trials under FDA Regulations. But this only involves the external microbes. Nevertheless, the University of Illinois in Champaign has created a tiny robot. This robot is not like the calculator that scientists in Israel created. It is designed to be implantable in humans, and give feedback. This tiny, implantable detector that could one day allow diabetics to monitor their glucose levels continuously—without ever having to draw a blood sample. the new sensors are based on single-walled carbon nanotubes: cylindrical molecules whose sides are formed from a lattice of carbon atoms. The idea is to exploit the nanotubes’ ability to fluoresce, or glow, when illuminated by certain wavelengths of infrared light—“a region of the spectrum where human tissue and biological fluids are particularly transparent,” They first coat the nanotubes with a “molecular sheath”: a one-molecule-thick layer of compounds that react strongly with a particular chemical—in this case, glucose. The mix of compounds is chosen so that the reaction also changes the nanotubes’ fluorescent response. They then illuminated the sample with an infrared laser and verified that the strength of the fluorescence from the buried sensor was directly related to the glucose concentrations in the tissue. But implanting small machines is simply inserting. It does not mean we have the ability to change anything. We are simply shoving around huge quantities of atoms. We must be able to pick one up at a time and place it in the precise location we want to. Scientists have performed a delicate surgical operation on a single living cell, using a needle that is just a few billionths of a meter wide. In order to manipulate cells, scientists currently use tiny injectors called micro-capillaries to introduce molecules such as proteins, peptides and genetic material into cells. But the shape of these micro-capillaries and a lack of accuracy in controlling them often results in fatal damage to the cell.
Measuring the forces as the nano-needle penetrated their interiors.
"To the best of our knowledge, the results demonstrated for the first time that solid material was inserted into a nucleus of such a small living cell with highly accurate positioning," the team writes in Nano-Letters."We can inject metabolic inhibitors into cells through a nano-needle allowing it to be accepted by the cell's metabolic pathways," said Dr Nakamura. "This cell surgery allows us to modify the cell's functions. "Dr Nakamura aims to use the technique on embryonic stem cells. It could be used to control the cells' differentiation - the process by which cells become, say, heart, kidney or liver cells - and how they proliferate - or divide. Another laboratory has gone even further. A team of German scientists has succeeded in creating what they call DNA ‘velcro’ to bind and then separate nanoparticles. University of Dortmund, Christof Niemeyer and his team used strands of artificial DNA University of Dortmund, Christof Niemeyer and his team used strands of artificial DNA. The advent of nanotubes coupled with optical materials has led us to be able to place markers within the cells we are attempting to study. The latest tests bode well on two counts. Not only did the nanotubes retain their optical signatures after entering the white blood cells, but the introduction of nanotubes caused no measurable change in cell properties like shape, rate of growth or the ability to adhere to surfaces. Although long term studies on toxicity and biodistributions must be completed before nanotubes can be used in medical tests, the new findings indicate nanotubes could soon be useful as imaging markers in laboratory in vitro studies, particularly in cases where the bleaching, toxicity and degradation of more traditional markers are problematic. When we combine the effects of nanotubes and markers we get a new nanotechnology-based technique could lead to a test for diagnosing the early signs of Alzheimer's disease. The Bio-Barcode-Assay can recognise ADDL, a protein that accumulates in the brains of sufferers. It is a million times more sensitive than conventional tests and could revolutionise disease detection. "We have done the first set of experiments that quantify the number of ADDLs in cerebrospinal fluid," Professor Mirkin said. ADDLs are protein bundles which attack nerve synapses in the brains of people with Alzheimer's. Professor Mirkin said it could also lead to a test to diagnose breast cancer by detecting the faint presence of a protein called PSA, normally associated with prostate cancer in men. It could also form the basis of a new test for HIV and other diseases in blood screening."The next exciting step would be to move to blood. If you detect it in blood, you have a huge win." To perform a Bio-Barcode-Assay, researchers select antibodies on the basis of the biomarker they need to detect in a solution. Some antibodies are fixed to magnetic particles while others are attached to spherical gold particles just 30 nanometres in diameter. Strands of DNA are fixed to the gold nanoparticle. When antibodies bind to a target biomarker, it becomes sandwiched between a magnetic particle on one side, and a gold particle and its strands of DNA on the other. Applying a magnetic field brings this entire "complex" out of solution. Researchers then release the DNA strands and use a DNA detection device to recognise their signature sequences. The dream of monitoring a patient's physical condition through blood testing has long been realized. According to Hood, the focus of medicine in the next few years will shift from treating disease -- often after it has already seriously compromised the patient's health-to preventing it before it even sets in.
Hood explains that systems biology essentially analyzes a living organism as if it were an electronic circuit. This approach requires a gigantic amount of information to be collected and processed, including the sequence of the organism's genome, and the mRNAs and proteins that it generates. The object is to understand how all of these molecular components of the system are interrelated, and then predict how the mRNAs or proteins, for example, are affected by disturbances such as genetic mutations, infectious agents, or chemical carcinogens. Therefore, systems biology should be useful for diseases resulting from genetics as well as from the environment.
"Patients' individual genome sequences, or at least sections of them, may be part of their medical files, and routine blood tests will involve thousands of measurements to test for various diseases and genetic predispositions to other conditions
"The yeast model taught us many lessons for human disease, For example, when yeast is perturbed either genetically or through exposure to some molecule, the mRNAs and proteins that are generated by the yeast provide a fingerprint of the perturbation. In addition, many of those proteins are secreted. The lesson is that a disease, such as a very early-stage cancer, also triggers specific biological responses in people. Many of those responses lead to secreted proteins, and so the blood provides a powerful window for measuring the fingerprint of the early-stage disease." with a sufficient number of measurements, "one can presumably identify distinct patterns for each of the distinct types of a particular cancer, the various stages in the progression of each disease type, the partition of the disease into categories defined by critical therapeutic targets, and the measurement of how drugs alter the disease patterns. The key is that the more questions you want answered, the more measurements you need to make. It is the systems biology approach that defines what needs to be measured to answer the questions."
you imagine the pathway toward predictive medicine rather than reactive medicine About 100,000 measurements on yeast were required to construct a predictive network hypothesis. The authors write that 100,000,000 measurements do not yet enable such a hypothesis to be formulated for a human disease. Need technologies, ranging from microfluidics to nanotechnologies to molecular-imaging methods.
Take for example nanosized quantum dots which light up when exposed to ultraviolet light making it possible to detect, target and kill cancer cells.
how a virus infects a cell. they tag them with some sort of transceiver and monitor the signal.
he started to examine quantum dots — nanoscale particles of semiconductors — as possible alternatives to the dyes.
they can last for over 48 hours The colour of light they emit can be changed by altering their size, with smaller dots emitting blue, green or yellow light and larger dots appearing orange, red or brown. “We can basically custom design the properties of the materials for whatever applications we need.”
Still, a major challenge remains. Quantum dots normally have a very oily surface the dots wouldn’t do well inside the water-based cellular environment. Chan is now looking for ways to modify the surface chemistry so that they interact with water-friendly molecules like proteins and DNA.
“When cells are diseased, they produce a unique set of proteins on their surface. If you find a matching molecule [to those proteins], you can take whatever you want to that site,” “Light can only penetrate so far into the body. You can screen for surface cancers but the deeper the cancer, the harder it is to screen using quantum dots as a technique.”
The quantum dots are made of potentially toxic heavy metals which, because of their size, can find their way into body structures that other materials can’t. “Nanotechnology has the potential to have many applications like contrast agents, biosensors and new diagnostic schemes,” how does your body deal with these materials
will also use the quantum dots to bring drug therapies to the disease site. Beyond cancer, could be used to detect pathogens such as malaria and HIV and he estimates that his quantum dots could be lighting up human disease within five to 10 years.

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