Featured Research

from universities, journals, and other organizations

Making Smart Drugs That Deliver The Right Kind Of Punch

Date:
March 25, 2004
Source:
University Of Michigan
Summary:
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. Researchers at the University of Michigan's Center for Biologic Nanotechnology hope to prevent that problem by developing "smart" drug delivery devices.

ANN ARBOR, Mich. -- 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.

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.

###

For more information:

Center for Biologic Nanotechnology---http://nano.med.umich.edu/

American Physical Society---http://www.aps.org/

Mark Banaszak Holl---http://www.umich.edu/~michchem/faculty/banaszakholl/

Bradford Orr---http://www.physics.lsa.umich.edu/department/directory/bio.asp?ID=254

Atomic force microscopy---http://stm2.nrl.navy.mil/how-afm/how-afm.html


Story Source:

The above story is based on materials provided by University Of Michigan. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan. "Making Smart Drugs That Deliver The Right Kind Of Punch." ScienceDaily. ScienceDaily, 25 March 2004. <www.sciencedaily.com/releases/2004/03/040324071839.htm>.
University Of Michigan. (2004, March 25). Making Smart Drugs That Deliver The Right Kind Of Punch. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2004/03/040324071839.htm
University Of Michigan. "Making Smart Drugs That Deliver The Right Kind Of Punch." ScienceDaily. www.sciencedaily.com/releases/2004/03/040324071839.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Fears Keep Guinea Hospitals Empty

Ebola Fears Keep Guinea Hospitals Empty

AP (Oct. 23, 2014) Fears of Ebola are keeping doctors and patients alike away from hospitals in the West African nation of Guinea. (Oct. 23) Video provided by AP
Powered by NewsLook.com
Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
More People Diagnosed With TB In 2013, But There's Good News

More People Diagnosed With TB In 2013, But There's Good News

Newsy (Oct. 22, 2014) The World Health Organizations says TB numbers rose in 2013, but it's partly due to better detection and more survivors. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins