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Nanovesicle Drug Slips Through the Blood-brain Barrier to Selectively Target Brain Cancer Cells

By BiotechDaily International staff writers
Posted on 30 Jul 2013
Nanovesicles composed of the detergent saposin C-dioleoylphosphatidylserine (SapC-DOPS) that kill cancer cells by binding to phospholipid phosphatidylserine (PtdSer) residues exposed on the cells' surface membrane have the ability to cross the blood-brain barrier and destroy brain cancers such as glioblastoma multiforme (GBM).

GBM is an aggressive brain tumor, fatal within one year from diagnosis in most patients despite intensive treatment with surgery, radiation, and chemotherapy. The migratory and microscopically invasive nature of GBM as well as its resistance to chemotherapy renders conventional therapies inadequate in its treatment. Furthermore, brain cancer cells are protected by the blood-brain barrier, which prevents conventional drugs from reaching the tumor.

Investigators at Ohio State University (Columbus, USA) treated two different brain cancer-mouse models with the nanotech drug SapC-DOPS. They reported in the June 4, 2013, online edition of the journal Molecular Therapy that SapC-DOPS selectively and effectively crossed the blood-brain tumor barrier to target brain tumors in vivo and that the targeting was contingent on the exposure of the anionic phospholipid PtdSer on the surface of the cancer cells.

SapC-DOPS binding induced apoptosis in the tumor cells, and increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS-induced killing efficacy. Tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. In addition to its cancer cell killing ability, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo.

“Few drugs have the capacity to cross the tumor blood-brain barrier and specifically target tumor cells,” said contributing author Dr. Balveen Kaur, associate professor of neurological surgery at Ohio State University. “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. 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.”

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Image: representation of a protein (blue), which contains three zinc fingers in complex with DNA (orange). The coordinating amino acid residues and zinc ions (green) are highlighted (Photo courtesy of Wikimedia Commons).

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