Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Making smart drugs that deliver the right kind of punch

24.03.2004


It’s a bitter irony of cancer therapy: treatments powerful enough to kill tumor cells also harm healthy ones, causing side effects that diminish the quality of the lives that are saved.


Nanoparticles depicted here among cells (green) show potential as targeted anti-cancer therapeutics.
Image: Paul Trombley, University of Michigan Center for Biologic Nanotechnology



Researchers at the University of Michigan’s Center for Biologic Nanotechnology hope to prevent that problem by developing "smart" drug delivery devices that will knock out cancer cells with lethal doses, leaving normal cells unharmed, and even reporting back on their success. A graduate student involved in the multidisciplinary project will discuss her recent work---zeroing in on characteristics that make the devices most effective---at a meeting of the American Physical Society in Montreal, Quebec, March 23.

The U-M group is using lab-made molecules called dendrimers, also known as nanoparticles, as the backbones of their delivery system. Dendrimers are tiny spheres whose width is ten thousand times smaller than the thickness of a human hair, explains physics doctoral student Almut Mecke. "These spheres have all sorts of loose ends where you can attach things---for example, a targeting agent that can recognize a cancer cell and distinguish it from a healthy cell. You can also attach the drug that actually kills the cancer cells. If you have both of these functions on the same molecule, then you have a smart drug that knows which cells to attack."


Mecke’s part of the project focuses on finding out how to get dendrimers into cancer cells without disrupting healthy cells. Previous work had shown that high concentrations of dendrimers are toxic---even without their cancer drug cargo---but no one was sure why that was or what could be done about it. Mecke used an atomic force microscope---a device so sensitive it can take pictures of single molecules---to spy on interactions between dendrimers and membranes similar to those that surround living cells.

The atomic force microscope is something like a phonograph with a motion detector attached to its needle. "As the tip moves across the surface, you can detect its movement each time it hits a bump," Mecke said. "If you scan the surface, line by line, and you record the motion of the tip, you get a three-dimensional image of the surface," where each bump is an individual molecule. By taking a series of pictures and putting them together into a movie, Mecke could watch dendrimers in action. What she saw was that "certain kinds of dendrimers disrupt membranes by literally punching holes in them."

That wasn’t the kind of punch the researchers wanted to deliver, so they tried tinkering with the dendrimers to see if they could prevent the damage. "Dendrimers usually have a charge, and so do cell membranes," Mecke said. "It’s the interaction between those charges that causes dendrimers to bind to cell membranes and disrupt them. What our group found is that if you modify the surface of the dendrimers chemically, they become uncharged" and no longer beat up on membranes.

Other research at the center showed that charged dendrimers are just as likely to enter healthy cells as cancer cells---a habit that makes them undesirable for cancer therapy---but that uncharged dendrimers don’t invade cells at all unless they have cancer-detecting targeting agents attached. "We can show that, with the targeting molecule attached, an uncharged dendrimer goes into cancer cells---and only cancer cells---and that’s what we want," Mecke said.

Early results of studies with mice show that the nanoparticle drugs do treat cancer effectively with fewer side effects than conventional chemotherapy drugs, just as the researchers had hoped. "It’s nice to see how everything fits together---my work with the model membrane, my colleague’s work with cell culture and other people’s work with the animal studies," Mecke said. Next, the researchers hope to add more functions to their dendrimer-drug devices, such as biosensors that can report on cancer cell death, indicating how successful a particular treatment has been.

Mecke collaborated on the work with U-M researchers Seungpyo Hong, a graduate student in the macromolecular science and engineering center; Anna Bielinska, a research investigator at the Center for Biologic Nanotechnology; Mark Banaszak Holl, associate professor of chemistry; Bradford Orr, professor of physics; and professor James Baker, director of the Center for Biologic Nanotechnology. Funding was provided by the National Cancer Institute’s Unconventional Innovations Program. The study is one of several major research programs under way in the U-M Center for Biologic Nanotechnology---a multi-disciplinary group that focuses on biologic applications of nanomaterials. Baker, the Ruth Dow Doan Professor of Biologic Nanotechnology in the U-M Medical School, is the study’s principal investigator.

Nancy Ross Flanigan | University of Michigan
Further information:
http://www.umich.edu/news/index.html?Releases/2004/Mar04/r032304

More articles from Health and Medicine:

nachricht New antibody analysis accelerates rational vaccine design
09.08.2018 | Scripps Research Institute

nachricht Distrust of power influences choice of medical procedures
01.08.2018 | Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

Im Focus: A molecular switch may serve as new target point for cancer and diabetes therapies

If certain signaling cascades are misregulated, diseases like cancer, obesity and diabetes may occur. A mechanism recently discovered by scientists at the Leibniz- Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and at the University of Geneva has a crucial influence on such signaling cascades and may be an important key for the future development of therapies against these diseases. The results of the study have just been published in the prestigious scientific journal 'Molecular Cell'.

Cell growth and cell differentiation as well as the release and efficacy of hormones such as insulin depend on the presence of lipids. Lipids are small...

Im Focus: Touring IPP’s fusion devices per virtual-reality viewer

ASDEX Upgrade and Wendelstein 7-X – as if you were there / 360° view of fusion research

You seem to be standing in the plasma vessel looking around: Where otherwise plasmas with temperatures of several million degrees are being investigated, with...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Ph.D. student develops spinning heat shield for future spacecraft

10.08.2018 | Physics and Astronomy

Investigating global air pollution

10.08.2018 | Life Sciences

The “TRiC” to folding actin

10.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>