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 Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>