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.