A researcher can use a microscope to see where and how much of the drug has been delivered because the probe emits a reddish color under special lighting or via MRI because of its optical and magnetic components.

As the drug testing continues, images can be taken over and over without any loss of optical or MRI signal. Researchers can then measure the size of the tumor and number of cancer cells that “light up” compared with the original untreated tumor.

This provides a way to determine whether the drug is doing what it is supposed to be doing in the targeted areas. The technique is much easier than the current process of removing treated cancer tumors and weighing them at regular intervals to determine the drug’s efficiency in an animal.

“Many people in my area have been studying this approach for years,” Santra said. “But we have now moved it into a live cell, not just in test tubes.”

Sudiptal Seal, the director of UCF’s NanoScience Technology Center and nanoscience scientist believes Santra’s research is significant.

“This is indeed a major breakthrough in Qdot research,” Seal said. “This new diagnostic tool will certainly impact the field of nanomedicine.”

Santra and his team used semiconductor Qdots to create the probe. Because of their small size and crystal-like structure, Qdots display unique optical and electronic properties when they get excited. These unique properties make them ideal for sustained and reliable imaging with special lights.

For this research funded by the National Science Foundation and National Institutes of Health, the UCF-led team used a superparamagnetic iron oxide nanoparticle core decorated with satellite CdS:Mn/ZnS Qdots which carried the cancer-fighting agent STAT3 inhibitor. The Qdot optical signal turned on when the probe bonded with the cancer cells.

“The potential applications for drug testing specifically for cancer research are immediate,” Santra said.

Dendrimers have been used to encapsulate drug molecules and serve as a delivery vehicle, but in the new study they were employed to capture circulating tumor cells by biomimicry — using nanotechnology to create artificial surfaces much like those in real cells.

“We want to take advantage of what nature gives us,” says Seungpyo Hong, lead researcher of the study, published in the journal Angewandte Chemie. “We want to create new biomimetic surfaces that will allow us to remove damaged cells from the blood.”

Hong, assistant professor of biopharmaceutical sciences at UIC, and his coworkers created a highly sensitive surface that enables multivalent binding — the simultaneous binding of many molecules to multiple receptors in a biological system. The biomimetic surface was created using dendrimers of seventh-generation polyamidoamine, or PAMAM, and the anti-epithelial cell adhesion molecule, or aEpCAM.

In the body, cancer cells can detach from a primary tumor and flow throughout the bloodstream, enabling them to seed distant new tumors. Rare and difficult to capture, only a few circulating tumor cells can be found in a milliliter of blood in a cancer patient. By comparison, the same volume of blood contains several million white blood cells and a billion red blood cells, Hong said.

Three breast cancer cell lines were used as circulating tumor cell models, with each used to compare the cell adhesion of the dendrimer surfaces to a linear polymer of polyethylene glycol. PEG is commonly used to bind molecules to improve the safety and efficiency of therapeutics.

The nano-scale PAMAM dendrimers were chosen because their size and surface dimension could accommodate multiple anti-epithelial cell adhesion molecules, Hong said. This enabled the multivalent binding, along with the physiological process of “cell rolling” induced by E-selectin, which mimics the process by which circulating tumor cells are recruited to the endothelia and enhances the surface sensitivity toward tumor cells.

The surface developed by the UIC research team demonstrated up to a million-fold increase in binding strength, and up to 7-fold increase in detection efficiency, as compared to the aEpCAM-coated PEG surface that is the current gold standard for circulating tumor cell detection.

Hong says this is the first study to capture the tumor cells on the surface exploiting the multivalent effect, which is most likely due to the spherical architecture of dendrimers. The research was selected as a “Hot Paper” byAngewandte Chemie and highlighted in Faculty of 1000 by Donald Tomalia, the inventor of PAMAM dendrimers.

The results demonstrate that the combination of nanotechnology and biomimicry has a “great potential to be applied for highly sensitive detection of rare tumor cells from blood,” Hong said.

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Thomas O’Neal

University of Central Florida’s Thomas O’Neal will be testifying Thursday, July 14, about the revolutionary nature of nanotechnology before the U.S. Senate Subcommittee on Science and Space.

The Subcommittee is part of the Senate’s Commerce, Science and Transportation Committee. Committee Chairman John Rockefeller IV invited O’Neal to provide his expert testimony as the group considers reauthorizing the National Nanotechnology Initiative. Sen. Bill Nelson will preside over the hearing, which begins at 10 a.m. in room 253 of the Russell Senate Office Building.

O’Neal, the associate vice president of the Office of Research and Commercialization at UCF, is the founder and executive director of the well-known UCF Business Incubation Program. He was asked to speak about how UCF has succeeded in technology transfer, industry partnerships and the overall impact on economic development.

“Central Florida is in many ways a model for how governments, the university and industry can work together to grow the companies that stimulate the economy,” O’Neal said. “The committee is interested specifically in how research in nanotechnology can be developed through systems like ours.”

O’Neal is president of the Florida Business Incubation Association and serves on the board of directors for the National Business Incubation Association. He is a leading U.S. proponent of business incubation and economic gardening efforts to stimulate local economic growth.

Lt. Gov. Jennifer Carroll

Florida Lt. Governor Jennifer Carroll will be at the Central Florida Research Park Research Pavilion today. She will meet with the EDC and visit the Nanoscience Technology Center. Tomorrow she’s off to visit SpaceX at the Kennedy Space Center.

The work, a collaboration between physicists and molecular neuroscientists at Oxford, shows that artificial DNA cages that could be used to carry cargoes of drugs can enter living cells, potentially leading to new methods of drug delivery.

A report of the research is published online in the journal ACS Nano.

The cages developed by the researchers are made from four short strands of synthetic DNA. These strands are designed so that they naturally assemble themselves into a tetrahedron (a pyramid with four triangular faces) around 7 nanometres tall.

The Oxford researchers have previously shown that it is possible to assemble these cages around protein molecules, so that the protein is trapped inside, and that DNA cages can be programmed to open when they encounter specific ‘trigger’ molecules that are found inside cells.

In the new experiment they introduced fluorescently-labelled DNA tetrahedrons into human kidney cells grown in the laboratory. They then examined the cells under the microscope and found that the cages remained substantially intact, surviving attack by cellular enzymes, for at least 48 hours. This is a crucial advance: to be useful as a drug delivery vehicle, a DNA cage must enter cells efficiently and survive until it can release its cargo where and when it is needed.

“We’ve demonstrated a 3D plasmon ruler, based on coupled plasmonic oligomers in combination with high-resolution plasmon spectroscopy, that enables us to retrieve the complete spatial configuration of complex macromolecular and biological processes, and to track the dynamic evolution of these processes,” says Paul Alivisatos, director of Berkeley Lab and leader of this research.

The development involves artificial proteins, bundles of peptide helices with a photoactive molecule inside. These proteins are arranged on electrodes, which are common feature of circuits that transmit electrical charges between metallic and non-metallic elements. When light is shined on the proteins, they convert photons into electrons and pass them to the electrode.

“It’s a similar mechanism to what happens when plants absorb light, except in that case the electron is used for some chemistry that creates energy for the plant,” Dawn Bonnell, director of the Nano/Bio Interface Center said. “In this case, we want to use the electron in electrical circuits.”

In many ways, life is like a computer. An organism’s genome is the software that tells the cellular and molecular machinery—the hardware—what to do. But instead of electronic circuitry, life relies on biochemical circuitry—complex networks of reactions and pathways that enable organisms to function. Now, researchers at the California Institute of Technology (Caltech) have built the most complex biochemical circuit ever created from scratch, made with DNA-based devices in a test tube that are analogous to the electronic transistors on a computer chip.

Engineering these circuits allows researchers to explore the principles of information processing in biological systems, and to design biochemical pathways with decision-making capabilities. Such circuits would give biochemists unprecedented control in designing chemical reactions for applications in biological and chemical engineering and industries. For example, in the future a synthetic biochemical circuit could be introduced into a clinical blood sample, detect the levels of a variety of molecules in the sample, and integrate that information into a diagnosis of the pathology.

“We’re trying to borrow the ideas that have had huge success in the electronic world, such as abstract representations of computing operations, programming languages, and compilers, and apply them to the biomolecular world,” says Lulu Qian, a senior postdoctoral scholar in bioengineering at Caltech and lead author on a paper published in the June 3 issue of the journal Science.

To build their circuits, the researchers used pieces of DNA to make so-called logic gates—devices that produce on-off output signals in response to on-off input signals. Logic gates are the building blocks of the digital logic circuits that allow a computer to perform the right actions at the right time. In a conventional computer, logic gates are made with electronic transistors, which are wired together to form circuits on a silicon chip. Biochemical circuits, however, consist of molecules floating in a test tube of salt water. Instead of depending on electrons flowing in and out of transistors, DNA-based logic gates receive and produce molecules as signals. The molecular signals travel from one specific gate to another, connecting the circuit as if they were wires.

When a protein doesn’t fold into its normal shape, it also doesn’t perform its normal functions. This disruption in behavior could lead to proteins that aggregate into plaques or deposits and become toxic to cells. In Alzheimer’s disease, aggregates of a protein called beta-amyloid form in the central nervous system, causing damage to cells in the brain and triggering dementia.

An analytical capability for measuring tiny clusters of these proteins—before irreversible damage occurs—would be a powerful tool in the early detection of Alzheimer’s and other misfolded protein diseases. However, despite significant research efforts, there are currently no diagnostic tools available to selectively detect small-scale aggregates of misfolded proteins in biological fluids, such as blood or spinal fluid.

“This collaboration illustrates how a biomedical problem can also be a nanoscience problem, in which a chemical reagent is needed to recognize partially aggregated proteins,” said Ron Zuckermann, Director of the Biological Nanostructures Facility at the Molecular Foundry, a nanoscience user facility at Berkeley Lab. “We were faced with the challenge of synthesizing a material that’s capable of specifically detecting this aggregated protein and not any of the other proteins in the blood.”