Navigation Links
Researchers hone technique to KO pediatric brain tumors

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
Washington University in St. Louis

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:
(Date:6/25/2016)... ... ... Austin residents seeking Mohs surgery services, can now turn to Dr. Jessica ... Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to include Mohs ... Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of Glenn Goldstein, ...
(Date:6/25/2016)... ... , ... First Choice Emergency Room , the largest network of independent ... Director of its new Mesquite-Samuell Farm facility. , “We are pleased to announce ... Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. , ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary of ... award to iHire in recognition of their exemplary accomplishments in worksite health promotion. , ... Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire was ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Those who have ... these feelings, many turn to unhealthy avenues, such as drug or alcohol abuse, as ... Michigan, has released tools for healthy coping following a traumatic event. , Trauma sufferers ...
(Date:6/24/2016)... ... 2016 , ... The Pulmonary Hypertension Association (PHA) learned during ... two significant new grants to support its work to advance research and patient ... recognizing patients, medical professionals and scientists for their work in fighting pulmonary hypertension ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... 2016 Revolutionary technology includes multi-speaker ... , industry leaders in advanced audiology and hearing aid ... Opn ™, the world,s first internet connected hearing aid ... devices.      (Photo: ) ... of ,world firsts,: , TwinLink™ - the ...
(Date:6/23/2016)... 2016 The vast majority of dialysis patients ... Treatments are usually 3 times a week, with treatment ... travel time, equipment preparation and wait time.  This regimen ... for patients who are elderly and frail.  Many elderly ... rehabilitation centers for some duration of time. ...
(Date:6/23/2016)... 23, 2016  Experian Health, the healthcare ... the patient payment and care experience, today ... products and services that will enhance the ... offerings. These award-winning solutions will enable healthcare ... compliant in an ever-changing environment and redefine ...
Breaking Medicine Technology: