@article{7cec304b78e244428f8377f4f1b3922a,
title = "Systemic delivery of SapC-DOPS has antiangiogenic and antitumor effects against glioblastoma",
abstract = "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.",
author = "Jeffrey Wojton and Zhengtao Chu and Haritha Mathsyaraja and Meisen, {Walter H.} and Nicholas Denton and Kwon, {Chang Hyuk} and Chow, {Lionel M.L.} and Mary Palascak and Robert Franco and Tristan Bourdeau and Sherry Thornton and Ostrowski, {Michael C.} and Balveen Kaur and Xiaoyang Qi",
note = "Funding Information: We thank Ray Takigiku, Charlie Cruze, and Ellen Monson for comments on the manuscript. Patents are pending for the intellectual property disclosed in this manuscript. We thank Luis Parada for Mut3 mice, Hong Wu for loxP-Pten mice, and Eva Lee for loxP-Trp53 mice. We thank Suzanne J. Baker for the use of quadruple cKO mice in this study. L.M.L.C. is a St. Baldrick's Foundation Scholar and is supported by a Distinguished Scientist Award from the Sontag Foundation. We thank Amanda N. White for flow cytometric experiment. This work was supported in part by 1R01CA158372 and New Drug State Key Project grant number 009ZX09102-205 (to X.Qi), 1R43 CA136017 and 2R44 CA136017 grants from National Institutes of Health-National Cancer Institute (to X.Qi and Kevin Xu). X.Qi is listed as an inventor on the patent for SapC-DOPS technology that is the subject of this research. Consistent with current Cincinnati Children's Hospital Medical Center policies, the development and commercialization of this technology has been licensed to Bexion Pharmaceuticals, LLC, in which Dr Qi, holds a minor (<5%) equity interest. The other authors declared no conflict of interest.",
year = "2013",
month = aug,
doi = "10.1038/mt.2013.114",
language = "English (US)",
volume = "21",
pages = "1517--1525",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "8",
}