Systemic delivery of SapC-DOPS has antiangiogenic and antitumor effects against glioblastoma

Jeffrey Wojton, Zhengtao Chu, Haritha Mathsyaraja, Walter H. Meisen, Nicholas Denton, Chang Hyuk Kwon, Lionel M.L. Chow, Mary Palascak, Robert Franco, Tristan Bourdeau, Sherry Thornton, Michael C. Ostrowski, Balveen Kaur, Xiaoyang Qi

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a nanotherapeutic which effectively target and destroy cancer cells. Here, we explore the systemic use of SapC-DOPS in several models of brain cancer, including glioblastoma multiforme (GBM), and the molecular mechanism behind its tumor-selective targeting specificity. Using two validated spontaneous brain tumor models, we demonstrate the ability of SapC-DOPS to selectively and effectively cross the blood-brain tumor barrier (BBTB) to target brain tumors in vivo and reveal the targeting to be contingent on the exposure of the anionic phospholipid phosphatidylserine (PtdSer). Increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS-induced killing efficacy, and tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. Apart from cancer cell killing, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo. Interestingly, unlike traditional chemotherapy, hypoxic cells were sensitized to SapC-DOPS-mediated killing. This study emphasizes the importance of PtdSer exposure for SapC-DOPS targeting and supports the further development of SapC-DOPS as a novel antitumor and antiangiogenic agent for brain tumors.

Original languageEnglish (US)
Pages (from-to)1517-1525
Number of pages9
JournalMolecular Therapy
Issue number8
StatePublished - Aug 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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