Navigation Links
Researchers hone technique to KO pediatric brain tumors
Date:7/14/2008

An interdisciplinary team of researchers at Washington University in St. Louis, led by Karen L. Wooley, Ph.D., James S. McDonnell Distinguished University Professor in Arts & Sciences, is a step closer to delivering cancer-killing drugs to pediatric brain tumors, similar to the tumor that Senator Ted Kennedy is suffering from.

Such tumors are often difficult to completely remove surgically; frequently, cancerous cells remain following surgery and the tumor returns. Chemotherapy, while effective at treating tumors, often harms healthy cells as well, leading to severe side effects especially in young children that are still developing their brain functions.

In an effort to solve this problem, the Wooley lab has developed polymeric nanoparticles that can entrap doxorubicin, a drug commonly used in chemotherapy, and slowly release the drug over an extended time period. By tuning the polymer composition, they were able to tailor the release rate of the drug and improve its solubility.

The work was published in Chemical Communications and supported by The Children's Discovery Institute of St. Louis Children's Hospital and by the National Heart, Lung and Blood Institute of the National Institutes of Health as a Program of Excellence in Nanotechnology.

With their approach, the Wooley lab was able to load more doxorubicin into the cores of the nanoparticles, compared with similar constructs.

" Typically, a polymeric micelle has three to four percent [drug] loading per nanoparticle mass. In our case, we achieved 18 to 19 percent for our nanoparticles," said Andreas Nystrom, Ph.D., a post-doctoral associate, supported by the Knut and Alice Wallenberg Foundation, who worked on the project.

However, the nanoparticles carrying the doxorubicin were not as effective at killing cancer cells compared to the neat drug, because in these initial nanoparticles, no targeting groups were included and also the entire drug payload of the nanoparticle is not released. The identification and attachment of targeting ligands onto the nanoparticles and the rate and extent of drug release are now what the researchers will concentrate on and seek to improve. Ligands in this application are comprised of peptides and antibodies that bind to specific cell receptors over-expressed in cancer cells.

The cell studies were performed in vitro by Zhiqiang (Jack) Xu, Ph.D., a post-doctoral associate, together with Professor Jeff Leonard, M.D., in the Department of Neurological Surgery and Professor Sheila Stewart, Ph.D., in the Department of Cell Biology and Physiology, each in the School of Medicine at Washington University. Ultimately, in vivo, the nanoparticles are expected to target the tumors through the use of active targeting ligands and also through passive diffusion, as particles are well known to be taken up selectively into tumors by a process called the enhanced permeability and retention effect. The amount of drug released from the nanoparticles "might be enough for the intended therapy, if side effects are limited by selective tumor targeting," Nystrom said.

For these drug-filled nanoparticles to be effective for treating brain tumors, one challenge remainsdecorating the nanoparticles with signatures that direct them to the tumors and away from healthy cells, a process known as tissue specific targeting. Once attached to the tumor, the nanoparticles can release their deadly contents, killing the cancer cells and leaving the healthy cells unharmed.

"Everything depends on getting the nanoparticle to the tissue (tumor) of choice," said Nystrom.

Wooley agrees. "We have been studying these nanoparticles for some time now as a platform technology, achieving high radiolabeling efficiencies and demonstrating variable bio-distributions through a collaboration with the laboratory of Professor Mike Welch, in the Department of Radiology," she said. " Now, we are poised to take advantage of the progress made to develop the particles for diagnosis and treatment of several diseases.

"In this latest work, the nanoparticles were designed with thermally tunable core properties to serve as a host system that retains drug molecules at room temperature and then releases the cargo at physiological temperature, with a controlled drug release profile. The results are highly promising and are allowing us to move forward to a fully functional, tumor-targeted drug delivery device. The key to making this happen is the interdisciplinary team of investigators, each of whom brings a different chemical, biological or medical expertise."


'/>"/>

Contact: Karen L. Wooley
klwooley@wustl.edu
314-935-7136
Washington University in St. Louis
Source:Eurekalert

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/19/2017)... ... 18, 2017 , ... The CHP suggests that California drivers can avoid hydroplaning ... down and increasing the space between themselves and other vehicles, according to a January ... Raymond R. Hassanlou notes that, rain or shine, drivers should always incorporate safe driving ...
(Date:1/19/2017)... ... January 19, 2017 , ... The 21st Century Cures ... **An FDAnews Webinar**, Jan. 26, 2016 — 1:30 p.m. – 3:00 p.m. ET, ... Century Cures Act in order to thrive this year? , The passage of the ...
(Date:1/19/2017)... ... 19, 2017 , ... Infinity® Massage Chairs announced today that Dan Grover has ... marketing strategies. Grover comes with a total of 15 years experience in consumer goods ... Executive Vice President of Direct Sales at Traeger® Wood Pellet Grills. , Grover ...
(Date:1/19/2017)... ... January 19, 2017 , ... ... lines and wrinkles. Few people know that popular cosmetic fillers can ... Buckley, who is medical director of the MilfordMD Cosmetic Dermatology Surgery & Laser ...
(Date:1/18/2017)... Charlottesville, Virginia (PRWEB) , ... January 18, 2017 , ... ... New studies are released almost daily linking gut health to chronic disease, mental health ... the New Year ” as an important resolution to consider. , For one Charlottesville ...
Breaking Medicine News(10 mins):
(Date:1/18/2017)... 2017 Research and Markets has announced the addition ... User - Global Opportunity Analysis and Industry Forecast, 2014-2022" report to ... Vital signs ... to reach $5,491 million by 2022, growing at a CAGR of 5.8% ... was the leading regional market in global vital signs monitoring devices ...
(Date:1/18/2017)...  Adaptive Sound Technologies, Inc. (ASTI), the leading supplier ... Hyatt Place Nashville/Downtown to deliver the best sleep experience ... machines in over two hundred of its guest rooms. ... of having a great stay is sleeping well," said ... Nashville/Downtown. "We,re pleased to be able to offer our ...
(Date:1/18/2017)... 2017   Regenicin, Inc. (OTC Bulletin Board: ... the development and commercialization of regenerative cell therapies to ... reported the Company,s operating results for 2016 and an ... the Company described in its recent 10-K filing with ... accomplishments. The Company,s contract laboratory completed its evaluation of ...
Breaking Medicine Technology: