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Nano drug crosses blood-brain tumor barrier, targets brain-tumor cells and blood vessels

Date:
July 17, 2013
Source:
Ohio State University Medical Center
Summary:
The blood-brain barrier protects the brain from poisons but also prevents drugs from reaching brain tumors. A preclinical study shows that an experimental nanotechnology drug called SapC-DOPS crosses the tumor blood-brain barrier, targets brain-tumor cells and retards growth of tumor blood vessels. The findings also show why the agent targets tumor cells and recommend the drug's further development as a novel treatment for glioblastoma.

Artist's rendering of brain (stock image). The blood-brain barrier protects the brain from poisons but also prevents drugs from reaching brain tumors. A preclinical study shows that an experimental nanotechnology drug called SapC-DOPS crosses the tumor blood-brain barrier, targets brain-tumor cells and retards growth of tumor blood vessels.
Credit: Alexandr Mitiuc / Fotolia

An experimental drug in early development for aggressive brain tumors can cross the blood-brain tumor barrier, kill tumor cells and block the growth of tumor blood vessels, according to a study led by researchers at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).

The laboratory and animal study also shows how the agent, called SapC-DOPS, targets tumor cells and blood vessels. The findings support further development of the drug as a novel treatment for brain tumors.

Glioblastoma multiforme is the most common and aggressive form of brain cancer, with a median survival of about 15 months. A major obstacle to improving treatment for the 3,470 cases of the disease expected in the United States this year is the blood-brain barrier, the name given to the tight fit of cells that make up the blood vessels in the brain. That barrier protects the brain from toxins in the blood but also keeps drugs in the bloodstream from reaching brain tumors.

"Few drugs have the capacity to cross the tumor blood-brain barrier and specifically target tumor cells," says principal investigator Balveen Kaur, PhD, associate professor of neurological surgery and chief of the Dardinger Laboratory of Neurosciences at the OSUCCC -- James. "Our preclinical study indicates that SapC-DOPS does both and inhibits the growth of new tumor blood vessels, suggesting that this agent could one day be an important treatment for glioblastoma and other solid tumors."

The findings were published in a recent issue of the journal Molecular Therapy.

SapC-DOPS (saposin-C dioleoylphosphatidylserine), is a nanovesicle drug that has shown activity in glioblastoma, pancreatic cancer and other solid tumors in preclinical studies. The nanovesicles fuse with tumor cells, causing them to self-destruct by apoptosis.

Key findings of the study, which used two brain-tumor models, include:

  • SapC-DOPS binds with exposed patches of the phospholipid phosphatidylserine (PtdSer) on the surface of tumor cells;
  • Blocking PtdSer on cells inhibited tumor targeting;
  • SapC-DOPS strongly inhibited brain-tumor blood-vessel growth in cell and animal models, probably because these cells also have high levels of exposed PtdSer.
  • Hypoxic cells were sensitized to killing by SapC-DOPS.

"Based on our findings, we speculate that SapC-DOPS could have a synergistic effect when combined with chemotherapy or radiation therapy, both of which are known to increase the levels of exposed PtdSer on cancer cells," Kaur says.

Funding from the NIH/National Cancer Institute (grants CA158372, CA136017, CA136017, F31CA171733) and a New Drug State Key Project grant (009ZX09102-205) helped support this research.


Story Source:

The above story is based on materials provided by Ohio State University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jeffrey Wojton, Zhengtao Chu, Haritha Mathsyaraja, Walter H Meisen, Nicholas Denton, Chang-Hyuk Kwon, Lionel ML Chow, Mary Palascak, Robert Franco, Tristan Bourdeau, Sherry Thornton, Michael C Ostrowski, Balveen Kaur, Xiaoyang Qi. Systemic Delivery of SapC-DOPS Has Antiangiogenic and Antitumor Effects Against Glioblastoma. Molecular Therapy, 2013; DOI: 10.1038/mt.2013.114

Cite This Page:

Ohio State University Medical Center. "Nano drug crosses blood-brain tumor barrier, targets brain-tumor cells and blood vessels." ScienceDaily. ScienceDaily, 17 July 2013. <www.sciencedaily.com/releases/2013/07/130717164413.htm>.
Ohio State University Medical Center. (2013, July 17). Nano drug crosses blood-brain tumor barrier, targets brain-tumor cells and blood vessels. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2013/07/130717164413.htm
Ohio State University Medical Center. "Nano drug crosses blood-brain tumor barrier, targets brain-tumor cells and blood vessels." ScienceDaily. www.sciencedaily.com/releases/2013/07/130717164413.htm (accessed July 25, 2014).

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