Posted on 10/01/2006 10:49:10 AM PDT by Founding Father
In an attempt to increase the sensitivity of cancer biomarker detection and to decrease the need for large samples from which to detect those molecules, a multi-institutional research team has shown that a “forest” of single-walled carbon nanotubes can be used to detect lower levels of the prostate specific antigen (PSA) than is possible using the current commercial assay. Moreover, this new system requires between 5 and 15 times less sample than does the commercial system.
James Rusling, Ph.D., at the University of Connecticut, led the research team that developed this new assay system. The investigators report their findings in the Journal of the American Chemical Society.
The investigators began by developing a method in which single-walled carbon nanotubes self-assemble into forests standing in upright bundles on a conductive surface. Chemically reactive groups on the ends of the nanotubes provide a place to which the researcher can attach enzymes or antibodies capable of reacting with or binding to specific biomolecules. As a demonstration in the current paper, the researchers use an antibody that binds to PSA. The researchers also create a second detection reagent by conjugating another PSA-binding antibody with individual carbon nanotubes and then attaching multiple molecules of an enzyme known as horseradish peroxidase to the carbon nanotubes.
The resulting system works as follows. A serum sample or fluid extracted from a tissue sample is added to the antibody-labeled nanotube forest. Any PSA in the sample binds to this antibody. After washing the nanotube forest, the second antibody, linked to the peroxidase-coated nanotube, is added and allowed to bind to the PSA molecules now captured on the nanotube forest. After a second round of washing, the researchers then apply a voltage to the device and add hydrogen peroxide. As the peroxidase enzyme converts hydrogen peroxide to water, the device produces an electrical signal proportional to the number of times this reaction occurs, which itself is a direct reflection of how much PSA is bound to the nanotube forest.
The investigators note that this system can detect PSA at levels as low as 4 picograms per milliliter (pg/mL) in a sample size of 10 microliters of serum. In comparison, the standard assay now used clinically has a detection limit of 10-100 pg/mL but requires a sample size of 50-150 microliters. In addition, this system was able to provide quantitative detection of PSA from laser microdissection tissue samples of 1,000 cancer cells, something that current technology cannot achieve.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers.” Investigators from Salve Regina University, the National Institute of Dental and Craniofacial Research, and the National Cancer Institute also participated in this study. An abstract of this paper is available through PubMed.
Experiments Show Promise of Nanoparticle Targeting
Investigators developing an inhalable nanoparticle for treating lung cancer have shown that a surface molecule found on malignant lung cells can serve as an effective target for improving drug delivery. The research team, led by Carsten Ehrhardt, Ph.D., of the University of Dublin, has published its results in the European Journal of Pharmaceutical Sciences.
Aiming to improve the performance of a nanoparticle formulation of the drug doxorubicin, the investigators decided to target a cell surface protein known as the transferrin receptor, which is involved in satisfying cellular demands for iron. To determine if this receptor was a suitable target, the researchers first quantified levels of the transferrin receptor on malignant and healthy lung epithelial cells. Their results showed clearly that malignant cells possessed far higher levels of this protein than did their healthy counterparts.
Next, the investigators prepared lipid-based, doxorubicin-loaded nanoparticles decorated with the molecule transferrin. When they compared cell uptake of these targeted nanoparticles with that of nanoparticles lacking transferrin, the researchers found that uptake of the targeted nanoparticles was far greater. More importantly, the targeted nanoparticles were far more toxic to malignant cells than were the untargeted nanoparticles. In addition, the targeted nanoparticles were more toxic to malignant cells than they were to healthy cells, suggesting that targeting the transferrin receptor could prove to be an effective means of improving the ability of anticancer nanoparticles to deliver drug specifically to tumor cells.
This work is detailed in a paper titled, “In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer.” Investigators from Saarland University, Philipps University, and the Völklingen Heart Centre, all in Germany, also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.
http://nanotechwire.com/news.asp?nid=3828 ********************************************************
New Method Creates Nanowire Detectors Exactly Where Needed
There seems to be little doubt among cancer researchers that new detection systems using nanowires and microfluidics hold the promise of providing a quantum leap in the detection of cancer-related molecules and genes. However, researchers also know that there are significant technical barriers that must be overcome to realize that promise, including the current difficulty in creating microfluidic devices built around nanowire detectors.
Now, a team of investigators at the Nanosystems Biology Cancer Center, one of eight NCI-funded Centers of Cancer Nanotechnology Excellence, has developed a method for creating conducting polymer nanowires in place within microfluidic circuits. The team, led by Hsian-Rong Tseng, Ph.D., of the University of California, Los Angeles, and James Health, Ph.D., of the California Institute of Technology, reported their work in the journal Chemical Communications.
The researchers create the nanowires using standard microelectrodes built into the microfluidics device specifically for the purpose of carrying out electrochemical reactions within the channels of the device. This allows them to use the microfluidic channels to introduce the precursor molecules, or monomers, needed to create the conducting polymer nanowires and trigger an electrochemical reaction at the exact place where the nanowires are needed to function as biomolecule detectors. This reaction causes the monomers to link to one another, forming the conducting polymer nanowires. This process can create two different types of polymer nanowires, one made of polyaniline, the other of polypyrrole. The chemical reactions are completed within 40 minutes.
Once formed, the nanowires can function immediately as detectors, with the electrodes used to form the nanowires now functioning as the circuitry that connects the nanowires to electrical signal recorders. The investigators demonstrate that these detectors are highly sensitive to changes in pH and to changing ammonia concentrations, though they note that these nanowires should be able to be used to detect a wide range of biomolecules.
This work, which was supported in part by the National Cancer Institute, is detailed in a paper titled, “Electrochemical fabrication of conducting polymer nanowires in an integrated microfluidic system.” An abstract of this paper is available through PubMed.
http://nanotechwire.com/news.asp?nid=3827 ********************************************************
All-At-Once Detection of Multiple Disease Markers
When pathologists examine tissue samples in order to diagnose cancer of the lymphatic system, they examine the relative amounts of a group of proteins known as Cluster of Differentiation markers. Typically, this is a painstaking process, but new findings from investigators at the National Cancer Institute (NCI) show that quantum dots may be able to greatly simplify the process for examining the entire panel of Differentiation markers at once.
Reporting its work in the journal Modern Pathology, a team of investigators led by Stefania Pittaluga, M.D., Ph.D., at the NCI, describe the use of antibodies linked to quantum dots, in combination with a technique known as multispectral imaging, to detect 11 Cluster of Differentiation markers in fixed human lymphoid tissue samples. The researchers attached quantum dots with unique emission spectra – the color of light they emit when irradiated with light – to each of 11 commercially available antibodies that target these Differentiation markers. A meticulous series of experiments identified which color quantum dot worked best for detecting each of the antibodies.
Using these matched antibody-quantum dot conjugates, the investigators then showed they could detect and quantify five pairs simultaneously in fixed human lymphoid tissue. They accomplished this task using a confocal fluorescence microscope, and the researchers note that the quantum dots produced a bright signal with little background staining. This signal was far more stable over time than that given off by standard fluorescent dyes, permitting the investigators to image the sample multiple times without any change in the observed signal.
The researchers note that while their study validates the development of multi-target quantum dot-based diagnostic systems, there are still many factors that need to be examined to optimize the use of these nanoscale beacons. However, given the payoff in terms of ultimate ease of use and increased sensitivity, such studies should be conducted in the near future.
This work, which was funded by the National Cancer Institute, is detailed in a paper titled, “Multispectral imaging of clinically relevant cellular targets in tonsil and lymphoid tissue using semiconductor quantum dots.” An investigator from George Mason University also participated in this study. An abstract of this paper is available through PubMed.
http://nanotechwire.com/news.asp?nid=3826
Great post!
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ping
Catholics!
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